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PubMed2005

Unraveling the origin of lymphocyte progenitors.

Lymphocytes are ultimately derived from hematopoietic stem cells, however the intervening steps that give rise to lymphocyte progenitors are still under intense investigation. In particular, whether a common lymphocyte progenitor serves exclusively as a lymphoid precursor, or whether this cell retains limited myeloid progenitor potential are addressed by Rolink and colleagues. This issue is highlighted by their identification within the bone marrow of early progenitors with lymphoid and myeloid developmental potential or EPLMs. How these cells fit into our current understanding of lymphocyte development, and how this new subset helps to further refine our view of the common lymphocyte progenitor are discussed.

Animals↗
PubMedDate not supplied

Non-cryopreserved, limited number (1 or 2) peripheral blood progenitor cell (PBPC) collections following GCSF administration provide adequate hematologic support for high dose chemotherapy.

Sixty-two patients with a variety of malignant diseases including 44 with breast cancer, seven with sarcomas, five with germ cell tumours, four with Hodgkin's disease and two with multiple myeloma received short duration, high dose chemotherapy, with non-cryporeserved peripheral blood progenitor cell rescue as treatment for malignancy. Limited, (one or two) peripheral blood precursor cell collections were performed following either cyclophosphamide, cyclophosphamide+GCSF or GCSF priming. Total nucleated cell and CD34+ cell yields were significantly higher with either of the two GCSF priming regimens as compared to cyclophosphamide only priming. Cell viability at the time or reinfusion was also enhanced by GCSF priming. Chemotherapy regimens included either high dose cyclophosphamide, mitoxantrone and VP16 (HD-CNV); high dose melphelan plus VP16; high dose BCNU, cyclophosphamide and VP16 (BCV); or high carboplatin, cyclophosphamide and VP16 (PCV) all given over 8-12 h. Non-cryopreserved blood progenitor cells, stored at 4 degrees C, were reinfused 24 h after completion of chemotherapy. Sixty-one of 62 patients showed hematologic recovery. Median time to hematologic recovery was significantly shorter for patients receiving GCSF primed cell collections. There was also significantly less hospitalization and antibiotic usage for patients receiving GCSF primed precursor cell collections. The addition of post chemotherapy GCSF did not, however, appear to enhance the rate of hematologic recovery. This study shows that simplified schedules for high dose chemotherapy administration together with simple precursor cell collection procedures provide safe and effective methods for administering myeloablative chemotherapy treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Uptake and metabolism of malate in neurons and astrocytes in primary cultures.

Uptake and oxidative metabolism of [14C]malate as well as its incorporation into aspartate, glutamate, glutamine, and GABA were studied in cultured cerebral cortical neurons (GABAergic), cerebellar granule neurons (glutamatergic), and cerebral cortical astrocytes. All cell types exhibited high affinity uptake of malate (Km 10-85 microM) with slightly higher Vmax values in neurons (0.1-0.2 nmol x min-1 x mg-1) than in astrocytes (0.06 nmol x min-1 x mg-1). Malate was oxidatively metabolized in all three cell types with nominal rates of 14CO2 production of 2-15 pmol x min-1 x mg-1. The oxidation of malate was only slightly inhibited by 5 mM aminooxyacetic acid (AOAA). In granule cell preparations [14C]malate was incorporated into aspartate and glutamate and, to a much less extent, into glutamine. This incorporation was blocked by 5 mM AOAA. Astrocytes exhibited slightly higher incorporation rates into aspartate and glutamate, but in these cells glutamine was labelled to a considerable extent. AOAA (5 mM) inhibited the incorporation by 60-70%. In cultures of cerebral cortical neurons, very low levels of radioactivity derived from [14C]malate were found in aspartate and glutamate, and GABA was not labelled at all. Glutamine had the same specific activity as glutamate, indicating that the low rates of incorporation of radioactivity into amino acids in this preparation is likely to exclusively represent metabolism of malate in the small population of astrocytes (5% of total cell number), contaminating the neuronal cultures. The findings suggest that exogenous malate to a quantitatively limited extent may serve as a precursor for transmitter glutamate in glutamatergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2007

Body composition, muscle strength deficits and mobility limitations in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Chronicity of muscle weakness from cancer and its treatment may be problematic, particularly in those treated for cancer during childhood. We compared body composition, muscle strength, and mobility between 75 adult survivors of childhood acute lymphoblastic leukemia (ALL) and expected values based on population normative data. METHODS: Subjects were young adults treated for childhood ALL between 1970 and 1986, selected randomly from participants in an ongoing study of cancer survivors. DeXA scans were performed to evaluate body composition, and myometry used to measure strength. Mobility was evaluated with the Timed Up and Go (TUG) and 2-min walk (TMW). One sample t-tests compared ALL survivors to population norms. RESULTS: Males had 4.5% and females had 2.3% more body fat than expected (expected males 21.5%, females 36.0%). Males were 76.7 Newtons and females were 58.6 Newtons weaker in quadriceps strength than expected (expected males 569.87 N, females 464.67 N). Males walked 100.88 m and females walked 85.38 m less on the TMW (expected values: males 304.23 m, females 276.26 m), and took longer to complete the TUG (males 5.82 vs. 2.84 sec, females 5.88 vs. 3.00 sec) than expected. Treatment with cranial radiation and current growth hormone (GH) deficiency were associated with lower body weakness among females. CONCLUSIONS: Young adult survivors of childhood ALL have strength and mobility deficits. Decreased strength may reduce ability to participate in physical activity, perpetuating fitness deficits in survivors of childhood ALL.

Adult↗
PubMed1996

The anti-Dextran response of scid mice transgenic for the heavy chain of a Dextran specific IgM antibody.

Mice homozygous for the scid mutation bear a severe defect in their ability to rearrange V(D)J gene segments to yield active genes for immunoglobulin and T cell receptor molecules. In older animals few clones of B and T cells can arise at random, a phenomenon called leakyness of the scid mutation. We established scid mice carrying as a transgene the rearranged heavy chain of the IgM/lambda1 antibody MOPC 104E with specificity for the alpha(1,3) glucosidic linkages in Dextran. Despite the scid defect one-third of these mice immunized with the thymus independent antigen Dextran at 2 weeks of age, and all of those immunized at 6 weeks responded with anti-Dextran antibodies bearing the lambda light chain. This indicates that despite the scid mutation these animals had at least once successfully rearranged their endogenous lambda1 light chain gene segments and harbor Dextran specific B cells. These mice thus provided for the first time the opportunity to study the immune response of B cells of a single specificity in an environment that should, as we shall argue, be devoid of regulatory B and T cells able to recognize the idiotype of the responding cells. One week after immunization the anti-Dextran response of 5- to 6-week-old mu-transgenic scid mice amounted to 30% of the response of mu-transgenic non-scid mice but in essence both responses followed the same kinetics, reaching antibody concentrations indistinguishable from each other 8 weeks after a single dose of Dextran. Furthermore, the ready response of young mu-transgenic scid mice to this antigen by employment of endogenously rearranged lambda1 light chains allowed experiments to be done to compare the frequency of lambda1 light chain rearrangements in mu-transgenic scid mice to that in mu-transgenic non-scid mice. This was done in limiting dilution assays counting B cell precursors responsive to mitogen and differentiating in vitro to produce antibodies toward Dextran. Specific precursors were reduced to about 1% in the spleen of mu-transgenic scid mice when compared to the spleen of mu-transgenic non-scid mice; those in the peritoneal cavity lymphocyte population were reduced to about 12%.

Animals↗
PubMed1995

trkC-mediated NT-3 signaling is required for the early development of a subpopulation of neurogenic neural crest cells.

Soon after they segregate from the neural tube, trunk neural crest cells disperse on two spatially and temporally distinct pathways. Only crest cells that migrate early and ventromedially give rise to neurons of the peripheral nervous system. It is also known that neural crest cell-derived populations require appropriate environmental cues early in development in order to generate neurons, and for the subsequent survival of differentiated neurons. We examined whether neurotrophin-3 (NT-3), a survival factor for subsets of peripheral neurons, is also involved in the regulation of neurogenesis by neural crest cells. First, we found that premigratory and migrating neural crest cells on the medial migration pathway of Embryonic Day 2.5 (E 2.5) embryos express mRNAs encoding multiple isoforms of the NT-3 receptor, trkC, as do cells in the neural tube and epithelial dermamyotome. On E4, a subpopulation of neurons in nascent sensory ganglia express trkC message. Second, we demonstrate that trkC mRNA is only expressed in neural crest cell populations that possess neurogenic potential. Third, we show that the presence of NT-3, during the initial development of cultured neural crest cells, is required for neurogenesis by a subpopulation of neurogenic neural crest-derived cells. These results suggest that a subpopulation of neurogenic neural crest cells expresses functional trkC receptors and requires the timely availability of NT-3 for their development before reaching their final embryonic locations. We suggest that developmental heterogeneity exists in the identity and requirements of neural crest cell subsets that harbor neurogenic potential. We also suggest that the "paradoxical" expression of trkC receptors by the somitic dermamyotome may, in fact, play a role in the exclusive development of crest-derived neurogenic precursors on the medial pathway by limiting the availability of NT-3 on the lateral pathway.

Animals↗
PubMed1995

Hormonal regulation of skin gland development in the toad (Bufo boreas): the role of the thyroid hormones and corticosterone.

At metamorphic climax, anurans develop skin glands that migrate from the epidermis into the dermis. Thyroxine (T4) stimulates skin gland differentiation and migration, and a previous study showed that corticosterone (Cort) treatment of larvae is inhibitory. The current study used histological analyses to address the mechanism of Cort's prevention of skin gland development. Two types of glands were observed in controls at metamorphic climax: The first type resembled granular glands found in adults and the second resembled mucous glands. Differential staining revealed that the two gland morphologies represented functionally distinct granular and mucous glands. Treatment of larvae from Gosner Stages 35-42 with Cort or the goitrogen, thiourea (Thio), caused a reduction in the number of mucous (P < 0.05) but not granular glands. The similarity in the effects of Cort and Thio suggested that Cort inhibited skin gland development indirectly by down-regulating the hypothalamo-pituitary-thyroid axis. T4 treatment of larvae reversed the effects of Thio (T4+ Thio-treated animals); however, animals treated with T4+ Cort had no skin glands of either type. Triiodothyronine (T3) treatment of larvae resulted in the complete absence of skin glands with a limited number of gland nests (epidermal precursors of dermal skin glands), but stimulated epidermal growth. T3+ Thio- or T3+ Cort-treated animals also completely lacked skin glands. These data suggest that T3 favors epidermal growth at the cost of skin gland differentiation. Furthermore, we suggest that Cort inhibits skin gland development indirectly through its enhancement of T4 to T3 conversions, and that inhibition of skin glands is caused by an increase in T3 resulting from Cort treatment.

Animals↗
PubMed1994

Precursor frequency analysis of bryostatin activated lymphocytes.

Bryostatin 1 (Bryo) is a potent activator of protein kinase C. When T cells are stimulated with Bryo and the calcium ionophore ionomycin (Io), they expand rapidly in low-dose IL-2 (20 U/ml). We have shown that Bryo/Io-activated T-cells from murine tumor-draining lymph nodes have striking antigen-specific antitumor efficacy in vivo. To account for the specificity despite using a nonspecific T cell activation method, it was postulated that the Bryo/Io combination might preferentially activate antigen-sensitized T cells. To test this hypothesis, an allogeneic response model was used. C57BL/6 mice were primed by intraperitoneal (ip) injection with DBA/2 mouse splenocytes. After 9 days, the C57BL/6 spleens were harvested and H-2d-specific cytolytic T lymphocyte (CTL) precursor frequency (PF) was determined by limiting dilution analysis (LDA). A portion of the same spleen cells was treated for 18 hr with Bryo/Io and expanded for 7 days in IL-2 (20 U/ml); the LDA was then repeated to analyze PF after expansion. The entire experiment was also done with responder and stimulator strains reversed (DBA/2 mice immunized with C57BL/6 cells). The resulting PF values were [table: see text] Normal spleen cells treated with Bryo/Io exhibited < 10% release vs the same targets at any effector:target ratio, ruling out nonspecific cytolysis after Bryo/Io. T lymphocytes or CD8+ T cells were selected from primed splenocytes and the PF values before and after Bryo/Io were analyzed. These data showed that the increase in PF after expansion could not be attributed to T cell or CD8+ cell enrichment alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Differential antigen recognition by T cells from the spleen and central nervous system of coronavirus-infected mice.

CD8+ cytotoxic T lymphocytes (CTLs) isolated from the central nervous system (CNS) of C57BI/6 mice acutely infected with mouse hepatitis virus, strain JHM (MHV-JHM), and analyzed in a direct ex vivo cytotoxicity assay recognize two epitopes (H-2Db- and H-2Kb-restricted encompassing amino acids 510-518 and 598-605, respectively) within the surface (S) glycoprotein. In contrast, CD8+ T cells isolated from the spleens of mice inoculated intraperitoneally with MHV-JHM and restimulated in vitro only respond to the H-2Db-restricted epitope. In this report, the preferential recognition of the H-2Db-restricted epitope is confirmed using splenocytes stimulated in vitro with either MHV-JHM-infected MC57 cells or with a cell line expressing the S protein and analyzed in secondary CTL assays. To determine whether these results represent a difference in epitope recognition between the spleen and CNS, secondary CTL assays were performed using spleen cells coated with peptides encompassing the CTL epitopes as stimulators. Under these conditions, both epitopes sensitized cells for lysis by spleen-derived CTLs, suggesting that both epitopes were recognized by splenic CD8+ T cells after infection in vivo. Furthermore, limiting dilution analysis indicated that the precursor frequency of splenic CD8+ T cells specific for both the H-2Kb- and H-2Db-restricted epitopes were not significantly different. Thus, the results suggest that in vitro stimulation of splenocytes specific for the H-2Kb-restricted epitope is inefficient after endogenous processing but that this inefficiency can be corrected if peptide is provided exogenously at sufficiently high concentrations. As a consequence, the results also show that cells responsive to both of the previously identified CNS-derived CD8+ T cell epitopes are present in the infected spleen at nearly the same frequency.

Animals↗
PubMed1983

Comparative changes in the 32P labeling of adenine and uracil nucleotides in the hypertrophying rat heart.

The turnover of cardiac adenine and uracil nucleotides was studied in the hypertrophying rat heart by means of the kinetics of incorporation of labeled phosphate into the alpha-phosphate groups of nucleotides. Cardiac hypertrophy was induced either by chronic isoproterenol treatment (5 mg X kg-1 body wt. daily, s.c.) or by abdominal aortic constriction. In both experimental models, although the labeling of alpha-P groups of adenine nucleotides was at first unmodified, the incorporation of [32P]Phosphate into uracil nucleotides was accelerated early and the stimulation maintained for several days. The intramyocardial concentration of UTP and uracil nucleotides rose during the early phase of hypertrophy, while the ATP and adenine nucleotide pools were depleted. All of these alterations were more pronounced in isoproterenol-treated animals than in those with aortic stenosis. In this experimental model (isoproterenol treatment), the hypertrophy develops faster and is accompanied by a larger increase in cardiac RNA concentration. Thus, the increase in the rate of synthesis of uracil nucleotides may be interpreted as an adaptative change of nucleotide metabolism in response to an increased requirement of precursors for RNA synthesis. The possible limiting role of pyrimidine nucleotides in the hypertrophic process is discussed.

Adenine Nucleotides↗
PubMed1984

Clonal analysis of helper and effector T-cell function in neonatal transplantation tolerance: clonal deletion of helper cells determines lack of in vitro responsiveness.

Mice rendered tolerant at birth of H-2 alloantigens display concordant in vivo and in vitro phenotypes: they fail to reject skin grafts bearing the tolerated antigens, and their lymphoid cells fail to participate in tolerogenspecific mixed lymphocyte reactions (MLRs) and cell-mediated lympholysis (CML). Tolerant animals normally reject third-party skin allografts and develop positive MLRs and CML to third-party antigens. It has been suggested that clonal deletion of antigen reactive cells is the basis for this spectrum of responses. To investigate further the basis for the lack of in vitro alloreactivity, we conducted limiting dilution studies with lymph node cells from adult mice tolerant of various H-2 disparities. When the frequencies of (a) cells responding to the tolerogen in MLR and (b) interleukin-2-producing cells against the tolerogen were determined, it appeared that both types of cells were functionally deleted, that is, the frequency of cells responding to tolerogen-bearing stimulator cells was identical with that of cells stimulated with syngeneic cells. On the assumption that cells from H-2 tolerant mice are deficient in helper cell activity toward the tolerogen, we performed CML cultures under conditions in which exogenous help was provided in the form of supernatants derived from concanavalin A stimulated rat spleen cell cultures. Lymphoid cells from H-2 tolerant mice generated significant cytotoxicity toward the tolerogen under these conditions, although the absolute level of killing was reduced compared with that of cells from normal mice. Limiting dilution assays confirmed that Tc precursors were present in tolerant mice, and that they were reduced to less than 10% of normal numbers; however, tolerogen-specific Tc precursors were present in frequencies significantly greater than self-reactive Tc precursors. These data indicate that a deletion mechanism operates in neonatal transplantation tolerance to reduce the clone size of all three categories of functional T cells assayed, but that its efficiency is greatest among cells destined to provide specific T-cell help. The absolute functional deletion of helper cells determines the in vitro CML unresponsiveness of lymphoid cells from tolerant mice, and may be a crucial factor in promoting the in vivo phenotype of skin allograft tolerance.

Animals↗
PubMed1976

Inhibition of apatite formation by phosphorylated metabolites and macromolecules.

Apatite formation from synthetic extracellular fluids is rate-limited both at the initial amorphous precursor deposition step and at the amorphous-crystalline transformation reaction. Nucleotide diphosphates and triphosphates and low molecular weight metabolites containing two attached ester phosphate groups all inhibited amorphous-crystalline conversion at concentrations of 10(-5) to 10(-6)M. Both native and synthetic polynucleotides as well as the phosphoproteins from rat dentin or egg yolk also inhibited crystal formation from amorphous calcium phosphate. In all cases, substantial amounts of inhibitor molecules were incorporated into the stabilized amorphous precipitates. Treatment of isolated, inhibitor-stabilized amorphous precipitates with hydrolytic enzymes such as alkaline phosphatase or papain reversed the inhibitory effect and permitted crystallization to proceed normally.

Alkaline Phosphatase↗
PubMed2005

Differential expression of monomeric and proteolytically processed forms of tartrate-resistant acid phosphatase in rat tissues.

Purple acid phosphatase (PAP), also known as tartrate-resistant acid phosphatase (TRAP), uteroferrin or type 5 acid phosphatase (Acp5) is synthesized as an N-glycosylated monomeric latent precursor, which can be processed by limited proteolysis to a disulfide-linked two-subunit form with increased enzyme activity. In this study, we disclosed that the proteolytically processed two-subunit form constitutes the major PAP/TRAP variant in monocytic cells in spleen, thymus, liver and colon. In addition significant expression of the monomeric PAP/TRAP, indicating a non-enzymatic function, was detected in epithelial cells of colon, lung and kidney. Interestingly, proteolytic processing alone did not activate the enzyme but rendered the enzyme more susceptible to activation by reductants. Thus, beside limited proteolysis, the subcellular redox state could also be a determinant of enzyme action in vivo. The co-localization of PAP/TRAP and the cysteine protease cathepsin L could suggest a role for cathepsin L in the in vivo proteolytic processing of PAP/TRAP in monocytic cells.

Acid Phosphatase↗
PubMed2006

Characterization of the T7 promoter system for expressing penicillin acylase in Escherichia coli.

The pac gene encoding penicillin acylase (PAC) was overexpressed under the regulation of the T7 promoter in Escherichia coli. PAC, with its complex formation mechanism, serves as a unique target protein for demonstration of several key strategies for enhancing recombinant protein production. The current T7 system for pac overexpression was fraught with various technical hurdles. Upon the induction with a conventional inducer of isopropyl-beta-D-thiogalactopyranoside (IPTG), the production of PAC was limited by the accumulation of PAC precursors (proPAC) as inclusion bodies and various negative cellular responses such as growth inhibition and cell lysis. The expression performance could be improved by the coexpression of degP encoding a periplasmic protein with protease and chaperone activities. In addition to IPTG, arabinose was shown to be another effective inducer. Interestingly, arabinose not only induced the current T7 promoter system for pac expression but also facilitated the posttranslational processing of proPAC for maturation, resulting in significant enhancement for the production of PAC. Glycerol appeared to have an effect similar to, but not as significant as, arabinose for enhancing the production of PAC. The study highlights the importance of developing suitable genetically engineered strains with culture conditions for enhancing recombinant protein production in E. coli.

Arabinose↗
PubMed1990

Amplification of the genes for both components of ribonucleotide reductase in hydroxyurea resistant mammalian cells.

Ribonucleotide reductase catalyzes the formation of deoxyribonucleotides from ribonucleoside diphosphate precursors, and is a rate-limiting step in the synthesis of DNA. The enzyme consists of two dissimilar subunits usually called M1 and M2. The antitumor agent, hydroxyurea, is a specific inhibitor of DNA synthesis and acts by destroying the tyrosyl free radical of the M2 subunit of ribonucleotide reductase. Two highly drug resistant cell lines designated HR-15 and HR-30 were isolated by exposing a population of mouse L cells to increasing concentrations of hydroxyurea. HR-15 and HR-30 cells contained elevated levels of ribonucleotide reductase activity, and were 68 and 103 times, respectively, more resistant than wild type to the cytotoxic effects of hydroxyurea. Northern and Southern blot analysis indicated that the two drug resistant lines contained elevated levels of M2 mRNA and M2 gene copy numbers. Similar studies with M1 specific cDNA demonstrated that HR-15 and HR-30 cell lines also contained increased M1 message levels, and showed M1 gene amplification. Mutant cell lines altered in expression and copy numbers for both the M1 and M2 genes are useful for obtaining information relevant to the regulation of ribonucleotide reductase, and its role in DNA synthesis and cell proliferation.

Animals↗
PubMed1987

Human B lymphocytes capable of spontaneous Ig production in short-term cultures. II. Relationship with the spontaneous DNA-synthesizing B cells.

It has been previously demonstrated that normal nonimmunized individuals possess circulating and tissular B cells, which are capable of spontaneous immunoglobulin (Ig) production in short-term (3 days) cultures. We have also observed the occurrence of low levels of [3H]thymidine uptake early in such cultures. This work analyzes the relationship between both spontaneous B-cell functions in vitro: Kinetics studies revealed that both activities were temporarily related, as spontaneous DNA synthesis was maximal from 8 to 12 hr, and declined thereafter, when spontaneous Ig secretion was first detected in the culture supernatant: The abrogation of DNA synthesis at the culture initiation or during the period of early proliferation, but not after 24 hr, inhibited subsequent IgG secretion. The B cells responsible for spontaneous DNA synthesis and IgG secretion exhibited similar low densities, since both were recovered in the 42.5-45% Percoll fractions, and identical large size as determined by 1g sedimentation procedure, and in tonsil, were equally reactive with the BA-2 mouse monoclonal antibody. Finally, limiting dilution analysis showed that the precursor frequencies of both cells under study were similar. These results suggest that spontaneous DNA synthesis and IgG production are carried out by the same subset of in vivo-preactivated lymphoblastoid B cells.

Antigens, Surface↗
PubMed1983

Automated colorimetric assay for T cell cytotoxicity.

A colorimetric method has been developed for detecting the lysis of target cells by cytotoxic T lymphocytes (Tc). The method entails incubating Tc cells with thioglycollate-induced macrophage targets and estimating macrophage survival at the end of the assay by staining viable macrophages with the dye neutral red. The method is substantially more sensitive than the 51Cr release assay and can be used to detect alloreactive Tc cells and H-2-restricted Tc cells against viruses, haptens and minor-H antigens. Furthermore, the assay is applicable to limit dilution analysis of Tc cell precursors. The method is cheap, avoids radioactive materials and by measuring optical densities with automated spectrophotometers developed for microELISA systems, results can be obtained 50-100 times faster than with the radioactive procedure.

Animals↗
PubMed1988

Oligoclonality of rheumatoid factors arising spontaneously in lpr/lpr mice.

Rheumatoid factors (RF) from individual mice of the MRL/lpr and C3H/lpr strains were examined with regard to target specificity and heavy chain class expression. It was found that MRL/lpr-derived RF preferentially recognize IgG2a target antibodies while C3H/lpr-derived RF exhibit a broader range of cross-reactivity. IgM RF represent only a minor proportion of the RF response in both strains. The IgG2a-specific RF produced by the lpr strains were found to consist of relatively equal proportions of IgG1, IgG2b, IgG3, and IgA antibodies. However, most of the RF produced by a single individual expressed the same heavy chain class and antigen-binding specificity. These results indicate that within an individual lpr mouse, circulating RF are derived from extensive expansion of a limited number of antigen-activated precursors.

Animals↗