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At least 19 recordsLinked to original sources
PubMed2026

A novel triple-knockout allogeneic BCMA CAR T-cell therapy (CT0590) for multiple myeloma: preclinical and phase 1 study.

Host-versus-graft reaction (HVGR) is a major challenge in allogeneic chimeric antigen receptor (CAR) T-cell therapy. To counter host natural killer (NK) cell attacks, we armored allogeneic, HLA-I-deficient, B-cell maturation antigen (BCMA)-targeting CAR T cells with an NKG2A CAR. In vitro and animal studies demonstrated that allogeneic CAR-NKG2A T cells effectively resisted host NK cell-mediated killing. BCMA and NKG2A dual-targeting allogeneic CAR T cells (CT0590) resisted killing by NK cells and showed robust antitumor activity in preclinical in vivo models. On the basis of these data, a first-in-human study enrolled 5 patients (4 with relapsed and refractory multiple myeloma [RRMM] and 1 with primary plasma cell leukemia [pPCL]). CT0590 was well tolerated and caused no dose-limiting toxicities, treatment-related death, or graft-versus-host disease. Three patients achieved confirmed responses, including 2 with stringent complete response (sCR). Notably, sCR in the patient with RRMM was still ongoing (duration of response >23 months) at the time of data cutoff, and sCR in the patient with pPCL lasted for 20 months. Both patients showed robust expansion of universal CAR T cells (maximum concentration of >280 000 copies per μg genomic DNA) and higher baseline NKG2A expression on NK cells than nonresponders. These results suggest that CAR-NKG2A technology may overcome HVGR, especially in patients with elevated NKG2A expression on NK cells. Further studies of CT0590 in RRMM and pPCL are warranted. This trial was registered at www.clinicaltrials.gov as NCT05066022.

Humans↗
PubMed2025

Novel antibodies for identification, selection, and manipulation of T cells expressing Whitlow linker-containing CARs.

BACKGROUND: The translational study of chimeric antigen receptor (CAR) T-cell function, persistence, immunophenotype, and spatial localization after infusion is crucial for understanding factors that influence clinical outcomes. However, research has been limited by a lack of optimized tools to reliably detect CAR-engineered cells. To address this, we developed a novel platform to generate monoclonal antibodies (mAbs) targeting a linker peptide incorporated in single-chain variable fragments (scFvs) of most CAR constructs. METHODS: Using recombinant proteins and scFv linker peptides as immunogens, we generated murine mAbs against the Whitlow linker peptide, capable of binding cells expressing Whitlow linker-containing CARs in both fresh and formalin-fixed paraffin-embedded (FFPE) tissues. We evaluated these antibodies in multiple in vitro translational applications relevant to CAR T-cell research and manufacturing. RESULTS: We identified five unique mAbs reactive against the Whitlow linker and characterized their binding properties and three-dimensional structural conformation. One clone was evaluated in depth, demonstrating comparable capacity to identify CAR T cells in peripheral blood relative to other methods using anti-idiotype antibodies or recombinant CAR-target proteins. In contrast to these reagents, the anti-Whitlow mAb detects cells expressing Whitlow linker-containing CARs with different antigen specificities, including those harboring the widely employed anti-CD19 FMC63-derived scFv as well as other scFvs, such as those targeting B-cell maturation antigen (BCMA) or CD33. Importantly, the anti-Whitlow mAb identified CAR T cells in situ in archival FFPE tissues, and a DNA-barcoded format enabled their spatial characterization and immunophenotyping in highly multiplexed immunohistochemistry. We also assessed the functional consequences of antibody binding on CAR T cells in vitro and demonstrated the feasibility of anti-Whitlow mAb-mediated selective enrichment of CAR-expressing T cells for potential utility in manufacturing workflows. CONCLUSIONS: Anti-Whitlow mAb clones exhibited distinct structural and functional properties that can be leveraged for multiple applications, providing versatile tools for detection, selection and manipulation of a broad range of clinical and preclinical CAR T-cell products.

Humans↗
PubMed2025

Timing Genomic Antigen Loss in Multiple Myeloma Treated with T Cell-Redirecting Immunotherapies.

UNLABELLED: Genomic antigen loss is a recurring mechanism of resistance to chimeric antigen receptor T-cell (CAR-T) and T-cell engagers (TCE) in relapsed/refractory multiple myeloma (RRMM). Yet, it remains unclear whether these events are acquired under treatment or merely selected from preexisting, undetectable clones. By leveraging chemotherapy mutational signatures as temporal barcodes within whole-genome sequencing data, we could time genomic antigen escape in 4 of 11 patients with RRMM. In all cases, the biallelic loss was driven by genomic events acquired after exposure to BCMA- and GPCR5D-targeted CAR-T/TCE and not present at baseline. Longitudinal digital PCR analysis corroborated that resistance mutations were undetectable at therapy initiation but emerged preceding relapse. Among 752 newly diagnosed patients, only 2.7% and 9% had monoallelic inactivation of TNFRSF17 and GPCR5D, respectively, with no biallelic loss. Our findings suggest limited utility of mutational screening prior to CAR-T/TCE while underscoring the importance of dynamic surveillance during therapy. SIGNIFICANCE: Multiple myeloma has been demonstrated to recurrently develop resistance to T-cell redirection via genomic antigen escape. By leveraging chemotherapy mutational signatures, we demonstrate that somatic antigen-escape mechanisms are uniformly acquired following treatment initiation and not selected from among preexisting clones, emphasizing the importance of dynamic longitudinal surveillance for their emergence. See related commentary by Kauer et al., p. 532.

Humans↗
PubMed2026

Treatment Decisions in Multiple Myeloma.

Revolutions in transplantation and targeted and immune therapies have transformed multiple myeloma from a disease with an associated survival of a few years into one for which functional cure is an emerging goal. This abundance of effective therapies has created clinical complexity. Here we provide a practical framework, anchored in trial evidence and informed by emerging biologic discoveries, for the navigation of treatment decisions across the disease spectrum. We outline how cytogenetic and genomic risk stratification, functional fitness, and measurable residual disease status individualize therapy in newly diagnosed disease, in which quadruplet induction therapy is now standard and the role of autologous transplantation is being reevaluated. Regarding relapse, we address the sequencing of B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates, emphasizing T-cell fitness and multiantigen targeting to counter exhaustion and antigen escape. We also consider early interception in high-risk smoldering myeloma. Throughout, we underscore that enrollment of patients in clinical trials should be considered in order to ensure continued progress.

Humans↗
PubMed1976

In vitro tolerance induction of neonatal murine B cells.

The susceptibility of neonatal and adult B lymphocytes to tolerance induction was analyzed by a modification of the in vitro splenic focus technique. This technique permits stimulation of individual hapten-specific clonal precursor cells from both neonatal and adult donors. Neonatal or adult BALB/c spleen cells were adoptively transferred into irradiated, syngeneic, adult recipients which had been carrier-primed to hemocyanin (Hy), thus maximizing stimulation to the hapten 2,4-dinitrophenyl coupled by Hy (DNP-Hy). Cultures were initially treated with DNP on several heterologous (non-Hy) carriers and subsequently stimulated with DNP-Hy. Whereas the responsiveness of adult B cells was not diminished by pretreatment with any DNP conjugate, the majority of the neonatal B-cell response was abolished by in vitro culture with all of the DNP-protein conjugates. During the 1st wk of life, the ability to tolerize neonatal splenic B cells progressively decreased. Thus, tolerance in this system is: (a) restricted to B cells early in development; (b) established by both tolerogens and immunogens; (c) achieved at low (10(-9) M determinant) antigen concentrations; and (d) highly specific, discriminating between DNP- and TNP-specific B cells. We conclude that: (a) B lymphocytes, during their development, mature through a stage in which they are extremely susceptible to tolerogenesis; (b) the specific interaction of B-cell antigen receptors with multivalent antigens, while irrelevant to mature B cells, is tolerogenic to neonatal (immature) B cells unless antigen is concomitantly recognized by primed T cells; and (c) differences in the susceptibility of immature and mature B lymphocytes to tolerance induction suggest intrinsic differences between neonatal and adult B cells and may provide a physiologically relevant model for the study of tolerance to self-antigens.

Age Factors↗
PubMed1975

Sequential expression of germ line genes in development of immunoglobulin class diversity.

Differentiation of B cells occurs in two discontinuous stages. Primary differentiation of stem cells to B lymphocytes in birds occurs exclusively in the lymphoepithelial bursa of Fabricius; the fetal liver may serve this function in mammals. In chickens both the size of the B-lymphocyte pool and the generation of precursors for cells secreting different immunoglobulin classes is controlled by the bursa. The latter process involves the sequential expression of genes coding for heavy chain constant regions in the order mu, gamma, alpha. The second stage of B-cell differentiation is antigen-driven, and involves proliferation and maturation of B lymphocytes to plasma cells. Ontogenetic development of different classes of B lymphocytes in mammals is orderly, independent of exogenous antigens, and occurs in the sequence mu, gamma, alpha. A developmental switch in expression of Ch genes, beginning with mu, has been experimentally verified. We favor the hypothesis that generation of class diversity of B lymphocytes occurs during the antigen-independent first stage of differentiation, and that the genetic switch in Ch gene expression follows the sequence mu leads to gamma leads to alpha, but evidence of these points remains inconclusive.

Animals↗
PubMed1975

Responsiveness of lymphoid precursors to polyclonal B-cell activators.

We have shown previously that in the differentiation of fetal liver cells to mature B cells in irradiated hosts, these cells sequentially gain responsiveness to the polyclonal B-cell activators dextran-sulphate (DxS), lipopolysaccharide (LPS), and purified protein derivative from tuberculin (PPD), in that order. In this paper we show that both fetal liver cells and adult bone marrow cells responded with proliferation to DxS, but not to LPS OR PPD. However, neither fetal liver nor bone marrow cells gave rise to detectable numbers of high-rate antibody-secreting cells on short-term stimulation by polyclonal B-cell activators. The lack of LPS and and PPD responses of fetal liver and bone marrow cells could not be ascribed to the presence of inhibitory cells, and the DxS-induced response in these cell populations was not dependent on adherent cells. However, LPS could inhibit the DxS response of fetal liver cells, possibly indicating that DxS-responsive cells are precursors to B cells. Direct evidence was provided that DxS activated B-cell precursors in bone marrow. Thus, this cell population became responsive to LPS after DxS prestimulation, as measured by DNA synthesis. Bone marrow cells, sequentially stimulated with DxS and LPS, contained increased numbers of cells with surface immunoglobulin, although no significant increase in numbers of antibody-secreting cells was obtained. These data indicate that DxS had the capacity to increase the rate of differentiation of B-cell precursors. Finally, we show that the sequential appearance of responsiveness in B-cell differentiation to polyclonal B-cell activators is not due to lack of accessory cells during early stages in maturation.

Animals↗
PubMed2026

Computational prediction of a multi-epitope Human Metapneumovirus vaccine candidate through integrated reverse vaccinology and pan-genomic approaches.

Human metapneumovirus (HMPV) is a primary cause of global respiratory infections yet no approved vaccine currently exists. This study computationally predicts a multi-epitope vaccine candidate using a diverse dataset of 65 HMPV sequences spanning five continents. Following the screening of lead proteins for antigenicity and virulence, fifteen highly conserved MHC-I, MHC-II and B-cell epitopes were prioritized. These were integrated with a putative L7/L12 adjuvant using optimized AAY, GPGPG, and KK linkers to design three constructs (HMPV_V1-V3). Structural validation identified HMPV-V2 as the lead candidate that exhibits a Z-score of-5.24 and 87.7% of residues in favored Ramachandran regions indicating excellent stereochemical quality and structural stability. In silico docking indicated a strong predicted binding affinity between HMPV-V2 and the TLR4 receptor (energy: -969.2). Immune simulations predicted a robust adaptive response characterized by high IgG1 titers, memory B-cell maturation, and a Th1-dominant cytokine profile. Furthermore, molecular dynamics simulations suggested exceptional structural integrity for HMPV-V2, maintaining a low RMSD of 8.213 and RMSF of 0.737 throughout the simulation. Optimized in silico cloning into the pET28a (+) vector indicated a high potential for protein expression in E. coli systems. While these findings provide a theoretically grounded blueprint for vaccine development, this study is entirely computational and lacks experimental validation. Further in vitro and in vivo testing is required to confirm the actual safety and immunogenicity of the proposed candidate.

Metapneumovirus↗
PubMed1975

B lymphocytes lacking surface IG in patients with immune deficiency: initiation of IG synthesis in culture in cells of a patient with thymoma.

A 64-year-old woman with a syndrome of thymoma, severe hypogammaglobulinemia, seemingly normal cell-mediated immunity and aplastic anemia, was found to have virtually no immunoglobulin- (Ig) bearing peripheral blood lymphocytes (PBL). However, 7.8 +/- 3.4% of the PBL were positive for another B-cell marker, the receptor for aggregated IgG, while the remaining cells bound sheep erythrocytes. Those cells which were aggregate-reactive appeared to be immature or incomplete B cells. Cultures of peripheral blood leukocytes from the patient in various serum-containing media were studied by 3 independent technics for the development of lymphocyte surface Ig and for Ig in the culture supernatants. In vitro the patient's cells were able to develop surface Ig in media supplemented with fetal calf serum (FCS) or normal serum; in media supplemented with autologous serum, the cells developed no surface Ig. During the cultures in FCS, human Ig determinants became detectable in the medium, and both medium and cell-surface Ig underwent a shift from mu determinants early in the culture period to gamma and alpha determinants later. The development of Ig on the cells was not inhibited by the presence of autologous serum if FCS was included in the medium. These data support the concept that a factor, missing from this patient's serum, is required at an early stage in the maturation of the B cell. A patient with X-linked agammaglobulinemia had a population of circulating lymphocytes with surface characteristics similar to the B cells of the thymoma case. In contrast, no Ig synthesis by this patient's cultured cells could be demonstrated, indicating a different level of block in the 2 cases despite their similarity at the level of the cell surface.

Agammaglobulinemia↗
PubMed1975

Development of surface immunoglobulins in the chicken.

B-cell maturation in the chicken has been evaluated by the appearance of membrane immunoglobulins on cells in the spleen, the thymus, the bursa and the bone marrow during enbryonic development and shortly after hatching. The majority of the bursa cells acquire demonstrable membrane immunoglobulin between days 16 and 18 of incubational age and show significantly increased amounts of membrane immunoglobulin between days 18 and 20, even though immunoglobulin-bearing cells can be found in the bursa as early as day 14 of enbryonic age. The spleen shows cells possessing immunoglobulin receptors can their membranes (Ig+) only after the bursa cells have reached full membrane immunoglobulin maturation as reflected in the number of Ig+ cells and the amounts of membrane immunoglobuline. The thymus is practically devoid of Ig+ cells in the embry and it is not clear whether there any Ig-+ cells in the bone marrow. There are two phenomena which stand out in the observations. One is that there appears to be a gradual increase in the quantity of quality of the surface immunoglobulins on individual cells with advance in the embryonic development as reflected in the gradual increase in the staining intensity. The other is that there appears to be a polar distribution of membrane immunoglobulin in some cells especially in younger embryos. This polar distribution is seen under conditions where immunoglobulin capping is prevented by inhibitors and where immunoglobulin capping is impossible, such as with monomeric Fab. Immunoglobulin capping has been found to occur readily in embryonic cells and under conditions which would normally inhibit capping in adult cells.

Animals↗
PubMed2025

Recipient-derived vs. donor-derived CAR-T-cell therapy in relapsed B-cell acute lymphoblastic leukemia patients after transplantation: A multi-center retrospective study.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cells have been demonstrated to be an effective treatment for relapsed B-cell acute lymphoblastic leukemia (B-ALL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells for CAR-T therapy can be derived from the peripheral blood (recipient) of the patient or donor. Despite having identical genomes, the different maturation environments of these T cells can lead to functional differences. This study aimed to compare the clinical outcomes of CAR-T cells derived from these two sources. METHODS: This multicenter, retrospective cohort study collected clinical data from 36 patients who experienced B-ALL relapse after allo-HSCT and received CD19 CAR-T cell therapy between January 2016 and October 2023 across seven centers. The primary endpoint was complete remission (CR)/CR with an incomplete hematologic recovery (CRi) rate at 28 days post-CAR-T cell infusion. Secondary endpoints included the 2-year overall survival (OS) rate, 2-year event-free survival (EFS) rate, incidence of graft-versus-host disease (GVHD), cytokine release syndrome (CRS), and CAR-T cell-related encephalopathy syndrome (CRES). RESULTS: A retrospective analysis was performed on 36 patients: 12 in the recipient group and 24 in the donor group. The recipient and donor groups showed no statistically significant differences in CR/CRi rates (83.3% vs. 100.0%, P = 0.105), 2-year EFS rates (50.8% vs. 51.6%, P = 0.617), or 2-year OS rates (49.5% vs. 63.6%, P = 0.215). In addition, the incidences of GVHD, CRS, and CRES did not significantly differ between the two groups. Further analysis within the donor group revealed 12 matched sibling donors (MSDs) and 12 haploidentical donors (HIDs). The 2-year EFS rate was statistically significantly greater in the HID group than in the MSD group (75.0% vs. 30.7%, P = 0.043), whereas no significant differences were observed in the CR/CRi rates, 2-year OS, or the incidence of GVHD, CRS, and CRES between these subgroups. CONCLUSIONS: Both recipient-derived and donor-derived CD19 CAR-T cell therapies are effective treatment options for B-ALL relapsed post-allo-HSCT patients. HID-derived CAR-T cells offer a longer EFS and may be considered the optimal choice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2400085297.

Adolescent↗
PubMed2026

Multimodal computational framework resolves B cell maturation in autoimmunity and ageing.

Identification of the origin of pathogenic immune cells is crucial for therapeutic interventions and diagnosis but pseudotime methods struggle to trace immune cells accurately. Current trajectory inference methods for B cell development and response in health and disease either ignore or underutilize antigen receptor sequence information, limiting their ability to resolve developmental pathways, particularly for pathogenic populations. Widely used methods such as Monocle 3 reconstruct developmental paths from transcriptomic similarity alone, discarding the features from immune receptors. Dandelion has combined the immune receptor features with transcriptomics but it struggles to simulate the trajectory path of B cells. Here we present ClonoTrace, a computational framework that integrates BCR sequence features with transcriptomic trajectory inference through gated fusion of multimodal embeddings. In fetal B cell development and germinal centre development, ClonoTrace demonstrates closer concordance with the canonical reference ordering than Monocle 3 and Dandelion. Applied to systemic lupus erythematosus, ClonoTrace indicates a memory B cell extrafollicular maturation route alongside the naïve B cell route, accompanied by induction of ZEB2 with a concomitant decline of BACH2 along the trajectory, as a candidate alternative route to pathogenic double negative 2 B cells (DN2) in systemic lupus erythematosus (SLE) patients. In healthy ageing, ClonoTrace resolved three candidate age-related B cell maturation routes, from naïve, IgM+ memory and switched-memory B cells, each passing through a DN2-associated transcriptional state that is ordered before age-associated B cells along the inferred trajectory. ClonoTrace's fate probability algorithm indicated that IgM+ memory B cell to ABC transition as the leading candidate age-associated transition, which may be distinct from SLE DN2 maturation. ClonoTrace provides a generalizable framework for receptor-informed trajectory inference, describing candidate developmental routes of pathogenic B cell populations in autoimmunity and ageing.

Humans↗
PubMed1975

Basement membranes: structural and biosynthetic considerations.

Basement membranes are extracellular matrices synthesized by a variety of cells including the basal cells of the epidermis; the respiratory, gastrointestinal, and glandular epithelium; the capillary endothelium; the epithelial cells of the glomerulus, the renal tubule, and the lens capsule; and the endothelium of Descemet's membrane. Basement membranes in the mature animal are free of lipids, DNA, and proteoglycans and are composed of dissimilar protein subunits. One of these is a procollagen-like molecule associated with a noncollagenous matrix glycoprotein. The proportion of the latter component varies among basement membranes. These various subunits are stabilized by hydrogen bonds, disulfide bonds, and aldehyde-derived cross-links which are so extensive that they render the basement membranes highly insoluble. Immunochemical studies indicate three distinct antigenic components which correspond to the collagenous moiety, its nonhelical extension, and the matrix glycoprotein. The collagen component of basement membranes, free of the nonhelical extension, is composed of three identical alpha-chains. It is highly rich in hydroxylysine, 3- and 4-hydroxyproline and contains 4 to 8 residues of half-cystine. It contains 38 residues of glucosyl-galactosyl-hydroxylysine per chain and minimal amounts of mannose, glucosamine, and fucose. Newly synthesized basement membrane collagen is secreted in the extracellular space as the precursor molecule "procollagen." This molecule does not undergo conversion to collagen but interacts with the matrix glycoprotein to give rise to the appropriate structure.

Amino Acids↗
PubMed1975

Cellular basis of the immune response.

Lymphocytes, the cells competent to initiate immune responses, can be divided into two major groups: thymus-derived or T cells responsible for "cellular immunity" (e.g. delayed hypersensitivity reactions) and bursa (or bursa-equivalent) derived or B cells which produce immunoglobulin (antibody) molecules and are involved in "humoral immunity". "Accessory" cells, such as monocytes (or macrophages), polymorphonuclear leucocytes and mast cells act in an auxiliary manner by facilitating antigen processing or presentation, or by liberating factors which modify the various manifestations of the immune response. A variety of interactions between T and B cells and between lymphocytes and accessory cells have been described in both cellular and humoral immunity. Antigen-activated T cells produce factors with various activities: some are involved in recruiting inflammatory cells, others activate macrophages and enhance their microbicidal activities, and others modify B-cell responsiveness either by facilitating or suppressing it. These factors are instrumental in T-cell regulation of immune responsiveness. Antibody produced by B cells also plays a role in immuno-regulation, acting either as an immunopotentiating influence or as a negative feedback, e.g. when complexed with antigen, turning off the response of T or B cells. A detailed knowledge of the precise manner in which cells involved in immunity are regulated is essential for an understanding of how the foetus, an essentially "foreign transplant", can survive to term in its immunologically mature "alien" host.

Animals↗
PubMed1975

Properties of bispecific rosette-forming cells. I.--Presence of T-lymphocyte markers.

Three T-cell markers have been used to determine the origin of bispecific rosette forming cells (RFC) observed after stimulation by two species of heterologous red cells. The inhibition by anti-theta serum (AOS), azathioprine (AZ) and anti-lymphocyte serum (ALS) of the majority of bispecific RFC indicates their T-cell origin. The study of their sensitivity to these inhibitors suggested that about half of the bispecific RFC belong to immature T1 cell subset and the other half to more mature T2 cells. Conversely, monospecific RFC include both B-celle RFC have characteristics different from monospecific RFC argues against the reaction of double RFC against a common antigenic determinant of the two erythrocyte types.

Animals↗
PubMedDate not supplied

Biology of isolate immunocytes. III. Fine immunocytological characterization of lymphoplasma cells.

A system for characterization of lymphoplasma cells based on ultrastructural, immunocytological and autoradiographic data is proposed. It is composed of six cell types and transitional forms. Any mouse lymphocyte can be classified within one of these forms and the lymphocytes of a lymphoid organ may be subdivided into populations of characteristic cells. The cell types are defined as follows: 1) the differentiated Ig lymphocytes which bear Ig at their surface, have a rough nuclear sap, a granular cytoplasm and often show mcrovilli at the cell surface; none of these lymphocytes incorporate thymidine and therefore this subpopulation can be considered as mature; 2) the differentiated plasmacytes have a well organized rough endoplasmic reticulum; differentiated plasmacytes are not 3H-thymidine labelled and this subpopulation is mature; 3) the differentiated T lymphocytes with theta-antigen at their cell surface contain a smooth endoplasmic reticulum, a developed Golgi apparatus and lysophagosomes; the differentiated T lymphocytes show no 3H-thymidine labelling and this subpopulation is also mature; 4) in the large lymphocytes without surface Ig nor theta-antigen, chromatin aggregate are intermingled to the nuclear sap and a large nucleolus is present; this subpopulation of lymphocytes, a number of which show usually 3H-thymidine labelling, is immature; 5) the small lymphocytes without surface Ig nor theta-antigen have a large nuclear cytoplasm ratio; like the large lymphocytes, this population is also immature, since a percentage of these cells usually incorporates thymidine; 6) small T lymphocytes are labelled by the theta-antigen marker; after antigenic stimulation some of them are found to incorporate thymidine. Transitional forms between two cell types are also observed. They are more numerous immunization. This system of cell characterization is an attempt to correlate structure with function of lymphocytes withing the T and B cell concept of experimental immunology.

Animals↗
PubMedDate not supplied

Polyfunctional antibodies. Their biology and inheritance.

It seems likely that immunoglobulins have evolved from some archetypal molecule and those forms which are useful to the animal have been retained. It is this entire population of antibodies which forms the humoral immune system and in such a system, not only the properties of individual antibody combining regions, but the properties of the multiprotein system as a whole, are important for the defences of the body against pathogens. Antibody combining sites may bind a disparate set of structurally related and unrelated ligands. This multispecificity can be biologically meaningful: the same clone can be stimulated by different antigens. In this sense, cell surface immunoglobulins are multifunctional. The major biological consequence of antibody multispecificity is overlapping binding functions within subsets of the total antibody repertoire. The most significant impact of this overlap is: (1) it reduces the number of V genes necessary to code for the total number of combining sites; (2) the cross-stimulation of clones by structurally related and unrelated antigens may be instrumental in the normal maintenance of immune responsiveness and in addition, it may explain the ability to respond to unusual and less ubiquitous antigens; (3) the antigenic history of the animal may contribute to the maturation of the immune response by cross-stimulation of pre-selected clones of antigen binding cells.

Animals↗