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Biomedical subjects

J Punnonen

Publications and source records attributed to J Punnonen.

At least 37 records · Page 2Linked to original sources
PubMed1997

IL-4 synergizes with IL-10 and anti-CD40 MoAbs to induce B-cell differentiation in patients with common variable immunodeficiency.

In the present study the phenotype and function of lymphocytes from patients with common variable immunodeficiency (CVI) were studied. Five out of 12 patients had abnormally low proportion of CD4+ T cells, but PBMC of these patients were capable of proliferating in response to polyclonal T-cell mitogens or PPD antigen. The phenotype of patients' B cells, as determined by expression of CD10, CD19 and CD34, was comparable to that of healthy controls. IL-4 and anti-CD40 MoAbs induced moderate B-cell differentiation in PBMC derived from patients with CVI, but the frequencies of Ig-secreting cells were generally at levels spontaneously observed in healthy controls. IL-10 was completely ineffective in inducing IgG-secreting cells in cultures of PBMC derived from patients with CVI even in the presence of anti-CD40 MoAbs, whereas high frequencies of Ig-secreting cells were induced under similar condition in cultures of PBMC derived from healthy controls. Importantly, when IL-4 was added to cultures stimulated with anti-CD40 MoAbs and IL-10, a very strong synergistic effect on the numbers of Ig-secreting cells and the levels of Ig secretion was observed in PBMC from both patients and controls. Moreover, the frequencies of Ig-secreting cells after activation with anti-CD40 MoAbs, IL-4 plus IL-10 in PBMC from some patients were comparable to those observed in PBMC from healthy controls. Taken together, these results indicate that B cells from patients with CVI have impaired capacity to differentiate into Ig-secreting cells in response to IL-10 and anti-CD40 MoAbs, and that this unresponsiveness can be restored by exogenous IL-4 in a proportion of the patients.

Adolescent↗
PubMed1997

Pro- and anti-inflammatory cytokines in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the accumulation of inflammatory cells into the synovium and the destruction of joints. Cytokines are important regulators of the synovial inflammation. Some cytokines, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-1, function by promoting inflammatory responses and by inducing cartilage degradation. Other cytokines, such as IL-4, IL-10 and IL-13, function mainly as anti-inflammatory molecules. Although anti-inflammatory cytokines are present in rheumatoid joints, in progressive RA their levels obviously are too low to neutralize the deleterious effects of proinflammatory cytokines. Inhibiting the action of proinflammatory cytokines by using specific cytokine inhibitors or anti-inflammatory cytokines is the basis for new therapies currently tested in patients with RA. Promising results on the use of neutralizing anti-TNF-alpha monoclonal antibodies in the treatment of RA have been reported. The results from a trial using recombinant IL-10 in the treatment of patients with RA are available in the near future and will be important in determining the therapeutic potential of this cytokine.

Antibodies, Monoclonal↗
PubMed1996

Interleukin-10 functions as an antiinflammatory cytokine in rheumatoid synovium.

OBJECTIVE: Interleukin-10 (IL-10) is an antiinflammatory cytokine that has been shown to play a role in rheumatoid arthritis (RA). We therefore investigated the effects of IL-10 on the function and phenotype of synovial fluid mononuclear cells (SFMC) derived from patients with RA. In addition, we studied the production of IL-10 in rheumatoid joints, and the role of endogenous IL-10 in the regulation of SFMC function. METHODS: The presence of IL-10 in rheumatoid joints was studied using IL-10-specific enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase- polymerase chain reaction (RT-PCR) techniques. The effects of recombinant human IL-10 or neutralizing anti-IL-10 monoclonal antibodies (MAbs) on both cytokine production and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry. The effect of IL-10 on proliferation of SFMC was determined by incorporation of tritiated thymidine. RESULTS: IL-10 was detected by ELISA in 22 of 23 SF samples, and was spontaneously produced by cultured SFMC. IL-10 messenger RNA was detectable in all 8 SFMC samples, as determined by RT-PCR. Neutralization of endogenously produced IL-10 by anti- IL-10 MAbs resulted in increased production of IL-1 beta, tumor necrosis factor alpha (TNF alpha), and granulocyte- macrophage colony-stimulating factor (GM-CSF) by SFMC, and in enhanced proliferation of SFMC. In particular, the production of TNFalpha was dramatically increased by anti-IL-10 MAbs. Moreover, the expression of HLA-DR molecules by SF macrophages was increased, and the expression of CD16 was decreased by anti-IL-10 MAbs. In contrast, addition of recombinant IL-10 significantly decreased the production of IL-1 beta, TNF alpha, and GM-CSF by SFMC, and decreased spontaneous and IL-2-induced proliferation of SFMC. Finally, IL-10 decreased HLA-DR expression and increased the expression of the Fc gamma receptors, CD16 and CD64, by SF macrophages. CONCLUSION: These data indicate that endogenously produced IL-10 functions as an immunoregulatory molecule in rheumatoid synovium. Importantly, exogenous IL-10 has potent antiinflammatory effects on SFMC, suggesting that IL-10 may be useful in the treatment of patients with RA.

Adult↗
PubMed1996

The presence of interleukin-13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis.

OBJECTIVE: To study the production of interleukin-13 (IL-13) in rheumatoid synovium and the effects of recombinant IL-13 on the phenotype and function of synovial fluid (SF) macrophages and T cells derived from patients with rheumatoid arthritis (RA). METHODS: The presence of IL-13 in SF was studied using an IL-13-specific enzyme-linked immunosorbent assay (ELISA); the production of IL-13 was studied in SF mononuclear cells (SFMC) by reverse transcriptase-polymerase chain reaction. The effects of recombinant IL-13 on cytokine production by and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry, respectively. The effect of IL-13 on the proliferation of SFMC was determined by 3H-thymidine incorporation. The production and the effects of IL-13 were compared with those of IL-4. RESULTS: IL-13 was present in 27 of 28 SF samples, and IL-13 messenger RNA (mRNA) was detectable in SFMC. Importantly, IL-13 levels were significantly higher than those of IL-4, and IL-13 protein and mRNA were expressed in several samples, although IL-4 synthesis was undetectable. Recombinant IL-13 significantly reduced the production of IL-1 beta and tumor necrosis factor alpha and the expression of CD16 and CD64 by SF macrophages, whereas the expression of HLA-DR and CD23 was increased. These effects on SF macrophages were similar to those observed with IL-4, but in contrast to IL-4, IL-13 had no growth-promoting effect on SF T cells. CONCLUSION: IL-13 is consistently present in rheumatoid synovium. The ability of exogenous IL-13 to decrease the production of proinflammatory cytokines by SFMC suggests that it may have therapeutic potential in the treatment of patients with RA.

Adult↗
PubMed1996

Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis.

OBJECTIVE: The levels of interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-10, and granulocyte-macrophage colony-stimulating factor were measured in the peritoneal fluid of 15 patients with endometriosis to characterize the type of immune response that occurs at the site of endometriosis. STUDY DESIGN: Cytokine levels in peritoneal fluid obtained during laparoscopy from 15 patients and 12 controls undergoing tubal ligation were determined by enzyme-linked immunosorbent assay. RESULTS: The mean levels of interleukin-6 in patients with endometriosis and controls were 797 +/- 407 pg/ml and 133 +/- 38 pg/ml, respectively (p < 0.02). Similarly, the mean concentration of interleukin-10 in peritoneal fluids of patients with endometriosis was significantly higher than that of controls (241 +/- 38 vs 128 +/- 21, p < 0.05). The levels of interleukin-2, interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating factor were not significantly different between the two study groups. CONCLUSIONS: The levels of interleukin-6 and interleukin-10 are increased in the peritoneal fluids of patients with endometriosis, suggesting enhanced macrophage activity in these patients. Increased interleukin-6 and interleukin-10 production may partially contribute to the disturbed immune regulation observed in patients with endometriosis.

Adult↗
PubMed1996

Expression of bcl-2 in rheumatoid arthritis.

Since defective apoptosis has been suggested to play a role in the development of autoimmune diseases, we have investigated the expression of the proto-oncogene bcl-2 in patients with rheumatoid arthritis (RA). The expression of bcl-2 was studied in peripheral blood (PB) and synovial fluid (SF) lymphocytes and synovial tissues (ST) from patients with RA using immunohistochemistry, flow cytometry and nucleic acid hybridization. Patients with reactive arthritis (ReA) or osteoarthritis (OA) and healthy individuals were used as controls. The expression of bcl-2 protein in PB lymphocytes and the expression of bcl-2 mRNA in PB mononuclear cells (PBMC) was similar in healthy controls and patients with RA. However, bcl-2 protein expression was significantly reduced in SF lymphocytes when compared to PB lymphocytes. Similar results were observed with lymphocytes from patients with ReA, and irrespective of whether total lymphocytes, T cells or different T-cell subsets were studied. In the synovial sections, the expression of bcl-2 was restricted to lymphocytes, and bcl-2+ cells were observed in the majority of samples from patients with RA, OA and ReA. These data indicate that the expression of bcl-2 is not increased in the lymphocytes or ST derived from patients with RA. Instead, decreased expression of bcl-2 protein in SF lymphocytes compared to PB lymphocytes was demonstrated. We suggest that bcl-2 does not play a significant role in the pathogenesis of RA.

Adult↗
PubMed1995

IL-4 induces germ-line IgE heavy chain gene transcription in human fetal pre-B cells. Evidence for differential expression of functional IL-4 and IL-13 receptors during B cell ontogeny.

The present study demonstrates that IL-4 induces germ-line IgE heavy chain (epsilon) gene transcription in human fetal splenic mononuclear cells; fetal bone marrow cells; highly purified sorted surface (s) mu+, CD10+, CD19+ immature B cells; and s mu-, cytoplasmic mu+, CD10+, CD19+ pre-B cells derived from human fetal bone marrow. Similar to observations in normal adult B cells, TGF-beta and IFN-gamma inhibited IL-4-induced germ-line epsilon RNA synthesis in fetal pre-B cells, whereas anti-CD40 mAbs and TNF-alpha had enhancing effects, suggesting that the general mechanisms regulating germ-line epsilon transcription in adult B cells and pre-B cells are similar. IL-13 also induced germ-line epsilon RNA synthesis in s mu+, CD10+, CD19+ immature B cells, but the level of transcription induced by IL-13 was significantly less than that induced by IL-4. Anti-CD40 mAbs strongly synergized with both IL-4 and IL-13 in inducing germ-line epsilon RNA synthesis by fetal immature B cells. Interestingly, IL-13 failed to induce germ-line epsilon RNA synthesis in s mu- pre-B cells even in the presence of anti-CD40 mAbs. These distinct effects of IL-4 and IL-13 suggest that functional IL-13R are expressed at a later stage of B cell ontogeny than IL-4R, and that IL-13, in contrast to IL-4, does not regulate pre-B cell differentiation. Given the fact that IL-4 production appears to be enhanced in atopic individuals, the capacity of IL-4 to induce germ-line epsilon transcription in human fetal immature B cells and pre-B cells suggests that commitment of B cell precursors to IgE-producing cells may occur during intrauterine life and may explain the increased IgE production in neonates with a family history of atopy.

Antigens, CD↗
PubMed1994

Lymphoid and myeloid differentiation of fetal liver CD34+lineage- cells in human thymic organ culture.

In this article, we report that the human fetal thymus contains CD34bright cells (< 0.01% of total thymocytes) with a phenotype that resembles that of multipotent hematopoietic progenitors in the fetal bone marrow. CD34bright thymocytes were CD33-/dull and were negative for CD38, CD2, and CD5 as well as for the lineage markers CD3, CD4, and CD8 (T cells), CD19 and CD20 (B cells), CD56 (NK cells), glycophorin (erythrocytes), and CD14 (monocytes). In addition, total CD34+ lineage negative (lin-) thymocytes contained a low number of primitive myeloid progenitor cells, thus suggesting that the different hematopoietic lineages present in the thymus may be derived from primitive hematopoietic progenitor cells seeding the thymus. To investigate whether the thymus is permissive for the development of non-T cells, human fetal organ culture (FTOC) assays were performed by microinjecting sorted CD34+lin- fetal liver cells into fragments of HLA-mismatched fetal thymus. Sequential phenotypic analysis of the FTOC-derived progeny of CD34+lin- cells indicated that the differentiation into T cells was preceded by a wave of myeloid differentiation into CD14+CD11b+CD4dull cells. Donor-derived B cells (CD19+CD20+) were also generated, which produced immunoglobulins (IgG and IgM) when cultured under appropriate conditions, as well as functional CD56+CD3- NK cells, which efficiently killed K562 target cells in cytotoxicity assays. These results demonstrate that the microinjection of fetal liver hematopoietic progenitors into fetal thymic organ fragments results in multilineage differentiation in vitro.

Antigens, CD↗
PubMed1994

IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by immature human fetal B cells.

In this study it is demonstrated that the novel T cell-derived cytokine IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by human immature B cells derived from fetal bone marrow (BM). IL-13 induced proliferation and IgM, total IgG, IgG4, and IgE synthesis when total fetal BM cells or highly purified s mu+, CD10+, CD19+ fetal B cells were cultured in the presence of anti-CD40 mAb or activated CD4+ T cells. Although the ratios of the different isotypes produced in response to IL-13 were similar to those induced by IL-4, the levels of Ig produced in response to IL-13 were generally 5- to 15-fold lower, indicating that IL-13 is less potent than IL-4. In addition, in co-cultures of fetal B cells and CD4+ T cell clones IL-13 was effective only in the presence of IL-7, which may be due to the fact that IL-13, in contrast to IL-4, does not act on T cells. IL-13- and IL-4-induced IgE synthesis by s mu+, CD19+ fetal B cells was enhanced by IL-6 and inhibited by IL-12, IFN-alpha, IFN-gamma, and transforming growth factor-beta, suggesting that IL-13 and IL-4 induce IgE synthesis via similar signaling pathways. Like IL-4, IL-13 also induced Ig production, including IgG4 and IgE synthesis, by highly purified s mu-, CD10+, CD19+ pre-B cells co-cultured in the presence of activated cloned CD4+ T cells and IL-7. However, in contrast to IL-4, IL-13 did not enhance CD23, CD40, and HLA-DR expression on cultured s mu- pre-B cells in the absence of other stimuli, suggesting that IL-13 alone does not activate pre-B cells. Taken together, our data indicate that IL-13 induces proliferation, Ig isotype switching, and Ig production by immature fetal B cells in the presence of costimulatory signals provided by activated CD4+ T cells or anti-CD40 mAb. IL-13 is another cytokine that, in addition to IL-4, can induce isotype switching to IgG4 and IgE synthesis in immature human B cells.

Antibody Formation↗
PubMed1994

CD40 ligand-CD40 interaction in Ig isotype switching in mature and immature human B cells.

The CD40 ligand (CD40L) is a member of the TNF family, and has emerged as a key molecule in the contact-mediated signal required for B cell activation and differentiation. The cloned CD40L expressed on heterologous cells, or in the form of soluble multimeric molecules, can directly activate B cells and, in conjunction with cytokines, can induce Ig isotype switching in naive B cells. Patients with hyper-IgM syndrome, which results from defective CD40L expression, generally have no circulating Ig, except for IgM, indicating that the CD40L is also important for Ig isotype switching, in vivo. CD40L does not play a role in B cell development and appears not to be required for human activation and differentiation. The presence of CD40L on cells other than T cells, the relatively broad distribution of its ligand CD40, and the ability of T cells to be co-stimulated via CD40L, indicates a broader role for CD40L-CD40 mediated intercellular communication.

Antigens, CD↗
PubMed1994

Effects of cis- and trans-urocanic acids on the secretion of interleukin-1 beta and tumour necrosis factor-alpha by human peripheral blood monocytes.

In order to investigate the mechanism of urocanic acid (UCA)-mediated immune modulation, we studied the effect of cis- and trans-UCA on interleukin-1 beta and tumour necrosis factor-alpha production by human peripheral blood monocytes, using immunospecific ELISA techniques. Trans-UCA augmented the interleukin-1 beta production and inhibited tumour necrosis factor-alpha production in a dose-dependent manner, whereas cis-UCA had no effect on the secretion of these cytokines by phorbol myristate acetate or lipopolysaccharide-stimulated monocytes. This is a novel example of trans-UCA mediating a biological effect, a finding earlier reported for cyclic adenosine monophosphate up-regulation in human fibroblasts by Palaszynski and coworkers and for human natural killer cell inhibition by ourselves. Our data suggest an important role for trans-UCA as an immunomodulator in the skin.

Dose-Response Relationship, Drug↗
PubMed1993

An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors.

Interleukin 4 (IL-4) and IL-13 share many biological functions. Both cytokines promote growth of activated human B cells and induce naive human surface immunoglobulin D+ (sIgD+) B cells to produce IgG4 and IgE. Here we show that a mutant form of human IL-4, in which the tyrosine residue at position 124 is replaced by aspartic acid (hIL-4.Y124D), specifically blocks IL-4 and IL-13-induced proliferation of B cells costimulated by anti-CD40 mAbs in a dose-dependent fashion. A mouse mutant IL-4 protein (mIL-4.Y119D), which antagonizes the biological activity of mouse IL-4, was ineffective. In addition, hIL-4.Y124D, at concentrations of up to 40 nM, did not affect IL-2-induced B cell proliferation. hIL-4.Y124D did not have detectable agonistic activity in these B cell proliferation assays. Interestingly, hIL-4.Y124D also strongly inhibited both IL-4 or IL-13-induced IgG4 and IgE synthesis in cultures of peripheral blood mononuclear cells, or highly purified sIgD+ B cells cultured in the presence of anti-CD40 mAbs. IL-4 and IL-13-induced IgE responses were inhibited > 95% at a approximately 50- or approximately 20-fold excess of hIL-4.Y124D, respectively, despite the fact that the IL-4 mutant protein had a weak agonistic activity. This agonistic activity was 1.6 +/- 1.9% (n = 4) of the maximal IgE responses induced by saturating concentrations of IL-4. Taken together, these data indicate that there are commonalities between the IL-4 and IL-13 receptor. In addition, since hIL-4.Y124D inhibited both IL-4 and IL-13-induced IgE synthesis, it is likely that antagonistic mutant IL-4 proteins may have potential clinical use in the treatment of IgE-mediated allergic diseases.

Antigens, CD↗
PubMed1993

Brequinar sodium, mycophenolic acid, and cyclosporin A inhibit different stages of IL-4- or IL-13-induced human IgG4 and IgE production in vitro.

We investigated the effect of cyclosporin A (CsA), mycophenolic acid (MPA), and brequinar sodium (BQ) on human IgG4 and IgE synthesis induced by IL-4 or IL-13. BQ inhibited IL-4 and IL-13-induced IgG4 and IgE synthesis in cultures of peripheral blood mononuclear cells (PBMC) or highly purified B cells costimulated by anti-CD40 mAbs in a dose-dependent fashion. CsA and MPA had either suppressive or enhancing effects depending on the concentrations tested. Interestingly, BQ inhibited IgG4 and IgE synthesis at concentrations of 10(-6)-10(-8) M, which did not affect T or B cell proliferation, indicating that the inhibitory effects of BQ on Ig production were not directly related to inhibition of T or B cell proliferation. In contrast, the inhibitory effects of MPA on Ig production were directly associated with inhibitory effects on T and B cell proliferation. CsA blocked T and B cell proliferation at the same concentration (10(-7) M) which enhanced IgG4 and IgE synthesis, indicating that reduction in T or B cell proliferation correlated with enhanced IgE production. CsA also inhibited CD40 ligand expression and IL-2, IL-4, IL-5, IFN-gamma, and GM-CSF production by activated CD4+ T cell clones, whereas MPA and BQ were ineffective, indicating that these compounds do not inhibit early events in T cell activation. Collectively, our data indicate that BQ, MPA, and CsA block different stages of the IgG4 and IgE production process. In addition, we observed that CsA and MPA, in contrast to BQ, at lower concentrations can also have potentiating effects on the production of these Ig isotypes.

Antigens, CD↗
PubMed1993

Human pre-B cells differentiate into Ig-secreting plasma cells in the presence of interleukin-4 and activated CD4+ T cells or their membranes.

Studies on human B-cell development have been hampered by the lack of reproducible culture techniques to induce pre-B cells to differentiate into Ig-secreting plasma cells. Here, we describe that highly purified surface (s) mu-, cytoplasmic (c) mu+, CD10+, CD19+ human pre-B cells derived from fetal bone marrow (BM) differentiate with high frequencies into Ig-secreting plasma cells, when cocultured with activated, cloned CD4+ T cells and with interleukin-4 (IL-4). Production of IgM, total IgG, IgG4, and IgE in pre-B-cell cultures was detected, indicating that the cells also underwent Ig isotype switching. Pre-B-cell differentiation occurred in the absence of BM stromal cells, IL-7, and stem cell factor (SCF). However, IL-7 significantly enhanced the levels of Ig produced, whereas SCF was ineffective. Neutralizing anti-IL-4 monoclonal antibodies (MoAbs) completely inhibited pre-B-cell differentiation showing the specificity of the reaction. Intact CD4+ T-cell clones could be replaced by membrane preparations of these cells, indicating that the costimulatory signals provided by the activated CD4+ T cells are contact-mediated. In contrast, anti-CD40 MoAbs failed to provide the costimulatory signal required for pre-B-cell differentiation, which may be related to the very low expression of CD40 on fetal BM B cells. Activated CD4+ T cells and IL-4 also induced s mu expression and Ig synthesis in cultures initiated with pre-B cells that had been preincubated in medium for 2 days, and from which spontaneously emerging s mu+ B cells were removed by using a fluorescence-activated cell sorter. These results support the notion that the Ig synthesis observed in pre-B-cell cultures was not caused by outgrowth and differentiation of cells that spontaneously matured into s mu+ B cells. In addition, IL-4 and CD4+ T cells strongly enhanced CD40 and HLA-DR expression on the majority of cultured pre-B cells, further indicating that CD4+ T cells and IL-4 activate bona fide pre-B cells. Taken together, these data indicate that activated CD4+ T cells and IL-4 can provide all the necessary signals required for human pre-B cells to differentiate into Ig-secreting plasma cells.

Antigens, CD↗
PubMed1993

IL-10 and viral IL-10 prevent IL-4-induced IgE synthesis by inhibiting the accessory cell function of monocytes.

In the present study it is demonstrated that IL-10 and viral (v)-IL-10 inhibit IL-4-induced IgG4 and IgE synthesis in cultures of PBMC from healthy nonatopic donors. The inhibition occurred at the mRNA level. IL-10 strongly reduced IL-4-induced expression of both germline and productive epsilon transcripts in PBMC. The inhibitory effects were completely neutralized, or IgG4 and IgE synthesis was even enhanced, by anti-IL-10 mAb, demonstrating the specificity of the reaction. IL-4-induced IgG4 and IgE synthesis by PBMC was monocyte dependent. IL-4 failed to induce IgG4 or IgE synthesis by monocyte-depleted PBMC, but the production of these isotypes was completely restored by reconstitution with autologous monocytes. However, monocytes preincubated with IL-10 for 24 h failed to provide the accessory signals required for IL-4-induced IgG4 and IgE synthesis, indicating that the inhibitory effects of IL-10 are indirectly mediated via monocytes. This notion was further supported by the finding that IL-10 and v-IL-10 failed to inhibit IL-4-induced IgE synthesis in the absence of monocytes, i.e., when highly purified B cells were cultured in the presence of anti-CD40 mAb or cloned activated CD4+ T cells. Moreover, IL-10 failed to inhibit IL-4-induced germline epsilon mRNA synthesis in highly purified B cells. The inhibitory effects of IL-10 could not be restored by exogenous TNF-alpha or IL-6, indicating that the inhibitory effects were not mediated through inhibition of production of these cytokines. This is compatible with the observation that monocytes preincubated with IL-10 did not inhibit IgG4 or IgE synthesis in a monocyte- and T cell-independent culture system, in which purified B cells were cultured in the presence of anti-CD40 mAb and IL-4. Collectively, these data indicate that IL-10 mediates a potent, monocyte-dependent, inhibitory effect on IL-4-induced IgG4 and IgE production by human PBMC.

Antigen-Presenting Cells↗
PubMed1993

Characterization of a novel CD2+ human thymic B cell subset.

In the present study, it is demonstrated that functionally mature B cells are present in human thymus early during fetal life. Interestingly, 46 +/- 7% of fetal and postnatal thymic CD19+ B cells co-expressed CD2. Adult peripheral blood or splenic B cells were CD2-, and < 5% of fetal BM or fetal splenic CD19+ cells expressed CD2, indicating that CD2 is expressed preferentially on thymic B cells. Fetal thymic CD2+ B cells have a mature phenotype, because they are CD20+, CD40+, and surface IgM+, but they lack CD34 expression. They are also functionally mature because total thymic cell populations or highly purified CD2+ thymic B cells underwent Ig isotype switching and differentiation into Ig-secreting cells in a similar fashion as conventional B cells after culturing in the presence of IL-4 and activated cloned CD4+ T cells and anti-CD40 mAb cross-linked to Fc gamma RII/CDw32 transfected into murine L cells (Fc gamma RII+/L). Engagement of CD2 on thymic B cells by LFA-3+ L cell transfectants, anti-CD2 mAb cross-linked to Fc gamma RII+/L, or a mitogenic combination of anti-CD2 mAb did not result in proliferation or Ig production under the present conditions. However, anti-CD2 mAb enhanced IL-4 dependent Ig-synthesis by thymic B cells in the presence of activated CD4+ T cells, but they were ineffective when the B cells were activated by anti-CD40 mAb, suggesting that the anti-CD2 mAb stimulated antibody production indirectly via CD4+ T cells. Similarly, IL-7 enhanced IL-4-induced Ig production in the presence of CD4+ T cells. This effect of IL-7 also appeared to be indirect because no enhancement in Ig levels was observed in cultures of purified thymic B cells. Collectively, our results indicate that functionally mature B cells are present in human thymus early during fetal life, and that thymic CD2+, CD19+, sIgM+ cells represent a subset of bona fide B cells, which can be induced to Ig isotype switching and Ig production in vitro in a similar fashion as conventional B cells.

Antibody Formation↗