Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “B-Lymphocyte Subsets”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2026

TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro.

T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells play critical roles in regulating the activity of the germinal center (GC), which is essential for the generation of high-affinity antibodies. In the GC, Tfh cells help B cells to proliferate and to differentiate into memory B cells and long-lived plasma cells. In contrast, Tfr cells, a specialized subset of regulatory T cells (Tregs), modulate the humoral immune response by suppressing excessive or autoreactive B-cell activity. Here, we established an in vitro differentiation protocol for mouse CD4⁺ T cells that yielded CXCR5⁺FoxP3⁺ Tfr cells that exhibited a Bcl6hiPD-1hiCD25loGITRint phenotype and were distinct from Treg and Tfh cells. Functionally, in vitro-generated Tfr cells potently suppressed Tfh cell-driven B-cell class switching to IgG1 and downregulated the expression of B-cell costimulatory ligands. While in vitro-generated Bcl6-deficient Tfh cells were impaired in providing help to B cells for efficient class switching to IgG1, in vitro-generated Bcl6-deficient Tfr cells failed to inhibit Tfh cell-driven B-cell class switching to IgG1. Mechanistically, we showed that Tfr cells emerged from FoxP3+ precursors in low-IL-2 environments through a TGF-β- and c-Maf-dependent pathway, allowing for reprogramming and reinforcement of the follicular regulatory cell program in CD4+ T cells in vitro.

Animals↗
PubMed2025

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age.

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20-75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across tissue sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages; age-associated effects were manifested by site and lineage for macrophages in mucosal sites, B cells in lymphoid organs, and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan.

Humans↗
PubMed1979

Antigenic marker on a functional subpopulation of B cells, controlled by the I-A subregion of the H-2 complex.

CBA/N mice have an X-linked recessive effect that results in the absence of a subpopulation of B cells carrying the Lyb3 surface marker. It has been shown previously that this marker is present on a mature subset of B cells in all mouse strains. In this paper the Lyb3+ B cell population in C57BL/6 mice was analyzed further. This subset of B cells selectively expresses a surface marker controlled by the I-A subregion of the H-2 complex. A cytotoxic antiserum recognizing this marker was raised by immunizing defective (CBA/N X C57BL/6)F1 male mice with C57BL/6 spleen cells. This antiserum also contained noncytotoxic, non-strain-restricted anti-Lyb3 antibodies. The possible functional relevance of this surface marker is discussed.

Animals↗
PubMed1978

Mechanisms of clonal abortion tolerogenesis. I. Response of immature hapten-specific B lymphocytes.

B lymphocytes with receptors specific for the hapten fluorescein (FLU) were prepared from the spleens of mice of various ages. For most experiments, a one-step fractionation procedure based on the adherence of FLU-specific cells to FLU-gelatin was used. For some experiments, a subset of higher FLU-binding capacity was prepared from the FLU-gelatin binding population through the use of the fluorescence-activated cell sorter (FACS). FLU-specific B cells were placed into microculture with either FLU(3.6)-human gamma globulin (FLU(3.6)HGG) or FLU(12)HGG usually for 24 h at 37 degrees C. The tolerogen was then removed and 0.1 mug/ml of a T-independent antigen, FLU-polymerized flagellin, was substituted. 3 days later, cells were harvested from the microcultures and assayed for FLU-specific plaque-forming cells to determine any reduction in clonable hapten-specific B cells which the tolerogenesis treatment might have induced. The results showed that with FLU(3.6)HGG, hapten-specific newborn B cells could be tolerized at 1,000-fold lower tolerogen concentrations than adult splenic B cells of equal antigen-binding capacity. The high-avidity subset was even more susceptible to tolerance induction. Tolerance could be induced within 8 but not within 2 h, and at lower tolerogen concentrations, longer periods of tolerogenesis were required for a given effect. Using a 24-h tolerogenesis phase, 50 percent reduction in clone frequency among newborn FLU-gelatin fractionated cells was achieved at 0.08 mug/ml of FLU(3.6)HGG. Tolerance induction in immature B cells was inhibited by the concomitant presence of a polyclonal B-cell activator, Escherichia coli lipopolysaccharide (LPS) but tolerance once induced, was stable to challenge with LPS. Tolerogenesis was hapten specific. The proportion of tolerizable cells in spleens decreased with increasing age, reaching 50 percent at around 9 days. FLUI(12)HGG proved a more powerful tolerogen than FLU(3.6)HGG. It had an effect on adult cells, 50 percent reduction in clone frequency being noted at around 1 mug/ml. However, and in contrast to results claimed for other T- independent systems, there still was a major difference between immature and mature B cells, the immature cells displaying much greater sensitivity to tolerogenesis.

Animals↗
PubMed1978

Activation of mouse lymphocytes by anti-immunoglobulin. II. A thymus-independent response by a mature subset of B lymphocytes.

Mouse spleen cells can be stimulated to proliferate in vitro by purified anti-mu or anti-gamma,kappa antibodies. These responses can be obtained in cell populations bearing membrane immunoglobulin (Ig), purified by the fluorescence activated cell sorter (FACS), but they are not observed in FACS-purified Ig- cell populations. Furthermore, treatment of spleen cell populations with anti-Thy 1.2 and complement does not impair the response, nor does addition of nylon wool-purified T lymphocytes enhance it. These results indicate that B lymphocytes respond to anti-Ig and that their response does not require T cells. On the other hand, cells from athymic nude (nu/nu) mice respond slightly less well to anti-mu than do cells from heterozygous littermate (nu/+) controls; nu/nu cells are almost unresponsive to anti-gamm,kappa and addition of nylon wool-purified T cells from nu/+ controls does not restore the response. This suggests that T lymphocytes or the thymus may control the appearance of cells responsive to anti-gamma,kappa. Responsiveness of normal mice to anti-mu does not appear until 4 wk of age and does not reach maximum levels until 8 wk of age. Acquisition of full responsiveness to anti-gamma,kappa is even more delayed. This, together with the failure of mice with the CBA/N B-cell defect to respond to anti-Ig, suggests that cells stimulated to proliferate by anti-Ig are a mature subset of B cells. Depletion of adherent cells by Sephadex G-10 treatment or by treatment with carbonyl iron and exposure to a magnetic field does not diminish anti-mu or anti-gamma,kappa responses, suggesting that the responsiveness does not require the presence of macrophages. Thus, activation of B-cell proliferation by anti-Ig appears to be a T-cell independent, macrophage-independent process in which membrane Ig plays a direct role in signal generation.

Animals↗
PubMed1979

Adaptive differentiation of murine lymphocytes. IV (Responder x nonresponder) F1 T cells can be taught to preferentially help nonresponder, rather than responder, B cells.

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder x nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.

Animals↗
PubMed1979

In vitro model for natural tolerance to self-antigens. Inhibition of the development of surface-immunoglobulin-negative lymphocytes into T-dependent responsive B cells by antigen.

Neonatal and adult splenic cell suspensions were labeled with fluorescein isothiocynate-anti-Ig and fractionated into surface-immunoglobulin- (s-Ig) positive and s-Ig-negative subpopulations by the fluorescence-activated cell sorter. The subpopulations were then tested by splenic focus assay for both frequency and tolerance susceptibility of clonable 2,4,-dinitrophenol (DNP) precursors. It was shown that both adult, and neonatal, s-Ig-negative subsets contained clonable DNP-specific B-cell precursors. However, because these precursors result in fewer clones secreting IgG, they appeared to be less mature than the s-Ig-positive precursors. In the absence of helper T cells, it was found that exposure of s-Ig-negative lymphocytes to tolerogen during the process in which they were acquiring surface receptors resulted in nearly total abrogation of potential DNP clones. This finding provides compelling evidence for clonal abortion.

Animals↗
PubMed1979

Functional analysis of T cells expressing Ia antigens. I. Demonstration of helper T-cell heterogeneity.

We have examined the expression of I-region antigens on functional subpopulations of murine T cells. A.TH anti-A.TL (anti-Ik, Sk, Gk) alloantiserum was raised by immunization of recipients with concanavalin A (Con A) stimulated thymic and peripheral T-cell blasts. In contrast to similar antisera made by conventional methods, the anti-Ia blast serum was highly cytotoxic for purified T lymphocytes. Moreover, it reacted in a specific fashion with T cells having particular functions. Treatment of keyhole limpet hemocyanin (KLH)-primed B10.A (H-2 alpha) T cells with this antiserum plus complement resulted in the elimination of helper activity for B-cell responses to trinitrophenyl-KLH. Inhibition was shown to be a result of the selective killing of one type of helper T cell whose activity could be replaced by a factor(s) found in the supernate of Con A-activated spleen cells. A second type of helper cell required for responses to protein-bound antigens appeared to be Ia-. By absorption and analysis on H-2 recombinants, at least two specificities were detectable on helper T cells; one mapping in the I-A subregion and a second in a region(s) to the right of I-J. In addition, the helper T cell(s) involved in the generation of alloreactive cytotoxic lymphocytes was shown to be Ia+, whereas cytotoxic effector cells and their precursors were Ia- with this antiserum. These results provide strong evidence for the selective expression of I-region determinants on T-cell subsets and suggest that T-cell-associated Ia antigens may play an important role in T-lymphocyte function.

Animals↗
PubMed1976

Activation of human lymphocyte subpopulations by rabbit anti-human beta2-microglobulin and by lipopolysaccharide.

Rabbit anti-human beta2-microglobulin (anti-beta2m) was found to increase DNA synthesis in peripheral blood lymphocytes (PBLs) and in cells from abdominal lymph nodes, spleen, tonsil, adenoid, appendix, and bone marrow. The response to anti-beta2m was highest in cells originating from abdominal lymph node, appendix, and spleen. These organs were shown to contain a high proportion of surface-Ig-positive cells. No response to anti-beta2m was seen in thymus cells or in B-cell-depleted lymphocyte populations. Lipopolysaccharide (LPS) increased DNA synthesis in spleen cells, bone marrow cells, tonsil cells, and, sometimes, in cells from abdominal lymph nodes but weakly or not at all in PBLs. To study whether anti-beta2m and LPS activated the same subpopulation of lymphocytes, cultures were exposed to both mitogens in various concentrations. The effect on DNA synthesis in spleen cells was almost additive. This may indicate that these two polyclonal B-cell activators (PBAs) stimulate mainly distinct subsets of B cells in spleen. On the other hand, these two mitogens have a synergistic effect on DNA synthesis in PBLs. Since anti-beta2m is the first described selective B-cell mitogen activating human PBLs, it might be of clinical importance in the functional characterization of lymphocyte subpopulations.

B-Lymphocytes↗
PubMed1977

Independent segregation of two functional markers expressed on the same B-cell subset in the mouse: the Mls determinants and LPS receptors.

Mice of the C3H/Tif strain display a mixed leukocyte reaction (MLR) with all H-2k strains carrying any of the known alleles of the Mls locus. In particular, C3H/Tif is incompatible with the related substrain C3H/HeJ, from which it also differs at the locus responsible for the recognition of lipopolysaccharides (LPS) as B-cell mitogens, and at the Mod-1 locus. Our genetic analysis indicates that the MLR incompatibility between these strains is not H-2-linked and segregates as controlled by a single locus, most probably identical to Mls, for which the C3H/Tif strain expresses a previously unidentified allele, Mlse. Moreover, segregation data show that this locus assorts independently of LPS responsiveness and that neither marker is closely linked to the Mod-1 locus in linkage group II.

Alleles↗
PubMed1979

Human B cell function in a polyclonally induced plaque forming cell system. Cell triggering and immunoregulation.

The use of a sensitive PFC assay against a specific antigenic determinant (SRBC) following polyclonal triggering of human lymphocytes has provided a unique insight into the complex mechanisms of triggering of human B cells. The system is under the strict regulation of a delicate balance between helper and suppressor influences reflecting in certain circumstances the activity of distinct subsets of immunoregulatory cells. Lymphoid cells in certain diseases characterized by disordered immunoregulation, when as system, may in effect be manifesting an abnormal expression of immunoregulatory mechanisms operable in normal immune responses. In vivo activation of lymphoid cells by PBAs may have an important role in disease states as well as in the subsequent in vitro expression of B cell function. Furthermore, it is quite possible that under certain circumstances some B cell responses which appear to be purely antigen-specific may be reflections of synergy between PBA substances and specific antigen. The use of PBAs as probes and sensitive PVC systems as assays has already proven fruitful in the dissection of the complex mechanisms of nonspecific B cell triggering in man and may indeed ultimately lead to an understanding of the mechanisms of specificity of immune reactivity.

Adrenal Cortex Hormones↗
PubMed1979

Structural and functional characteristics of hairy cells.

Morphological, cytochemical, immunological and ultrastructural studies were performed on peripheral blood mononuclear cells from a patient with hairy-cell leukemia. Immunofluorescence studies showed a very strong intensity of fluorescence and indicated that hairy cells had monoclonal surface-membrane immunoglobulins (SmIg) actively produced by the cells. An unusual spontaneous SmIg redistribution induced by antibodies was also noted. Immunoultrastructural studies demonstrated that antibody-induced redistribution of SmIg on hairy cells is in form of a singular polar cap and that the cell membrane is rapidly cleaned of the complexes by endocytosis. The behavior of hairy cells regarding several membrane markers, mitogen stimulation and antibody-induced cytotoxicity suggests that hairy projections could represent the expression of a functional stage common to different lymphocyte subpopulations, or alternatively, a marker of a peculiar subset of B lymphocytes.

Antibodies, Neoplasm↗
PubMed2025

Serum proteomics reveals high-affinity and convergent antibodies by tracking SARS-CoV-2 hybrid immunity to emerging variants of concern.

The rapid spread of SARS-CoV-2 and its continuing impact on human health has prompted the need for effective and rapid development of monoclonal antibody therapeutics. In this study, we investigate polyclonal antibodies in serum and B cells from the whole blood of three donors with SARS-CoV-2 immunity to find high-affinity anti-SARS-CoV-2 antibodies to escape variants. Serum IgG antibodies were selected by their affinity to the receptor-binding domain (RBD) and non-RBD sites on the spike protein of Omicron subvariant B.1.1.529 from each donor. Antibodies were analyzed by bottom-up mass spectrometry, and matched to single- and bulk-cell sequenced repertoires for each donor. The antibodies observed in serum were recombinantly expressed, and characterized to assess domain binding, cross-reactivity between different variants, and capacity to inhibit RBD binding to host protein. Donors infected with early Omicron subvariants had serum antibodies with subnanomolar affinity to RBD that also showed binding activity to a newer Omicron subvariant BQ.1.1. The donors also showed a convergent immune response. Serum antibodies and other single- and bulk-cell sequences were similar to publicly reported anti-SARS-CoV-2 antibodies, and the characterized serum antibodies had the same variant-binding and neutralization profiles as their reported public sequences. The serum antibodies analyzed were a subset of anti-SARS-CoV-2 antibodies in the B cell repertoire, which demonstrates significant dynamics between the B cells and circulating antibodies in peripheral blood.

Humans↗
PubMed1975

Casein-induced experimental amyloidosis. V. The response of lymphoid organs to T and B mitogens.

Functional and morphologic studies were performed on the lymphoid organs of inbred CBA/J mice receiving chronic casein administration. In the spleen, this regimen produces marked reticuloendothelial proliferation between 8 and 16 injections (preamyloid phase) and amyloid deposition between 16 and 24 injections. No amyloid was found in the thymus, lymph nodes, and bone marrow of these animals. Phytohemagglutinin and concanavalin A lymphocyte responses as measured by 3-H-thymidine incorporation were reduced in the spleen and lymph node of preamyloid animals but demonstrated partial recovery during the amyloid phase. Phytohemagglutinin and concanavalin A stimulation of thymic cells was significantly increased during both stages of amyloid induction, although the histologic studies revealed a marked involution of the thymic cortex. Lipopolysaccharide stimulation of spleen cells was normal in preamyloid and amyloid animals whereas in lymph node and bone marrow lipopolysaccharide responses were significantly decreased. The findings suggest a selective removal of subsets of T cell populations in the spleen and thymus and migration of B cells from bone marrow to the spleen during experimental amyloidosis.

Amyloidosis↗
PubMed1978

Antigen-initiated B lymphocyte differentiation. XIV. Nonspecific effects of antigen stimulation cause proliferation in the "pre-progenitor" subset of primary B cells.

The effect of specific and nonspecific stimuli on the cycle status of subsets of primary B lymphocytes was assessed by preinjecting donor CBA mice 1 to 2 days previously with various substances, and then incubating the isolated spleen cells with high specific activity 3H-TdR before assay. AFC-progenitor activity was assessed as a response to NIP-POL antigen, either by adoptive transfer to irradiated recipients or by cell culture. Previous studies showed these assays reflected the activity of different subsets of B cells, termed "pre-progenitors" (adoptive assay) and "direct progenitors" (culture assay). Most functional primary B cells, whether assayed in culture or by adoptive transfer, were not initially in rapid cell cycle in normal adult mice. However, nonspecific stimulation for 1 day caused NIP-specific adoptive transfer IgM AFC-progenitors to enter rapid cell cycle. This effect was independent of T cells and not related to the antigenicity of the stimulus: particulate peritoneal irritants were the most effective stimulants. In contrast to adoptive transfer results. AFC-progenitors assayed in cell culture were unaffected by nonspecific stimuli, but were activated into cell cycle by specific antigen.

Animals↗
PubMed1979

Subsets of malignant lymphomas in children related to the cell phenotype.

We studied the lymphomatous cells of 39 children presenting with the classical features of malignant lymphoma. Twenty-two had T lymphoblasts. We could classify these patients into three subsets: The T lymphoblasts from children group 1 displayed antigen(s) shared by a thymocyte subpopulation, had terminal deoxynucleotidyl transferase (TDT), but no affinity for peanut agglutinin (PNA). The T lymphoblasts from children group 2 lacked the thymocyte antigen(s), had no TDT, but showed affinity for PNA. The T lymphoblasts from children group 3 displayed mature T-cell antigens, had no TDT, and no affinity for PNA. Children from the three groups were similar in terms of clinical presentation, age and sex distribution, and cell morphology; however patients from the three groups might have a different prognosis. Fourteen children had B lymphoblasts that, in half of the cases, had affinity for Helix pomatia agglutinin. Three patients had lymphoblasts lacking specific marker. Two of them had cells displaying an antigen found on common acute lymphoblastic leukemia cells and had TDT.

Adolescent↗