Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A
Open accessAbstract
In the present report, we have investigated the in vitro differentiation of surface(s) sIgD+ and sIgD- human B cells into Ig-secreting cells in response to various stimuli. sIgD+ B cells homogeneously expressed some of the antigens identifying mantle zone B cells, but lacked expression of germinal center markers, thus confirming that the B cell populations positively selected on the basis of sIgD expression were highly enriched for naive B lymphocytes. Conversely, sIgD- B cells expressed some of the antigens specifically associated with germinal center B cells. T cell-independent differentiation of sIgD+ and sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII (CDw32 L cells). In this experimental system, sIgD+ B cells were exclusively proned for IgM synthesis, whereas sIgD- B cells produced IgG, IgM, and IgA. Both the human and viral forms of interleukin 10 (IL-10) strongly increased the Ig secretion by sIgD+ and sIgD- B cells simultaneously activated through sIgs and CD40. IgM and IgG constituted the predominant Ig isotype produced by sIgD+ and sIgD- B cells, respectively, in response to IL-10. sIgD+ B cells could be induced for IgA synthesis upon co-culturing with transforming growth factor beta (TGF-beta) and IL-10, in the presence of an anti-CD40 monoclonal antibody presented by the CDw32 L cells. In contrast, TGF-beta suppressed the IL-10-mediated IgG, IgM, and IgA secretions by sIgD- B cells. sIgD+ B cells could not be induced for IgA synthesis by TGF-beta and IL-10 after crosslinking of their sIgs, suggesting that ligation of CD40 was one of the obligatory signals required for commitment of naive B cells to IgA secretion. Limiting dilution experiments indicated that the IgA-potentiating effect of TGF-beta was due to its capacity to increase the frequency of IgA-producing cells, most likely as a consequence of class switching. Taken together, our data strongly suggest that TGF-beta is involved in the regulation of IgA isotype selection in humans.
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IL-10 induces the growth, differentiation, and secretion of IgGs by B cells.
“Of particular interest is that IL-10 inhibits the production of IFN-γ by Th1 and NK cells, and induces the growth, differentiation, and secretion of IgGs by B cells (61, 62).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [61]
The Summary (p. 671) reports that IL-10 increased immunoglobulin secretion by human B cells activated through surface immunoglobulin and CD40; IgG was the predominant isotype from the sIgD− subset. The Discussion (p. 681) also describes IL-10 as a B-cell growth and differentiation factor. The claim omits the activation conditions and implies IgG secretion by B cells generally, whereas the naive sIgD+ subset predominantly produced IgM. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTGF-β is a powerful anti-inflammatory cytokine that acts on many target cells and tones down the inflammatory effects of TNF, IL-1β, IL-2, and IL-12.
“Together with IL-10, TGF-β is another powerful anti-inflammatory cytokine that acts on many target cells and tones down the inflammatory effects of TNF, IL-1β, IL-2, and IL-12, etc. (61, 67, 68).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [61]
The Results (Fig. 3) show that TGF-β suppresses IL-10-induced immunoglobulin secretion in one subset of human B cells, while enhancing IgA secretion in another. The paper does not establish the broader claim that TGF-β acts on many target cells or tones down inflammatory effects of TNF, IL-1β, IL-2, and IL-12. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIL-10 inhibits IFN-γ production by Th1 and NK cells.
“Of particular interest is that IL-10 inhibits the production of IFN-γ by Th1 and NK cells, and induces the growth, differentiation, and secretion of IgGs by B cells (61, 62).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [61]
The Results passage headed “Human IL-10 Enhances Ig Synthesis from Activated sIgD+ and sIgD− B Cells” concerns immunoglobulin production, not IFN-γ production by Th1 or NK cells. Searches for the claimed inhibition and for related cell and cytokine terms found no passage in our copy that addresses it. (LLM, conf=0.72)
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- Authors
- Defrance, T., Vanbervliet, B., Brière, F., Durand, I., Rousset, F., & Banchereau, J.
- Affiliations
- Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1992-03-01
- Volume
- 175
- Issue
- 3
- Pages
- 671-682
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2119142
- OpenAlex
- W2065712492
- Cited by
- 638
- References
- 0
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 9 · 2015: 18 · 2014: 12 · 2013: 8 · 2012: 14
- FWCI
- 19.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- IL-10, TGF-beta, IgA secretion, naive B cells, CD40 stimulation, class switch recombination, germinal center B cells
- MeSH terms
- Antibody-Producing Cells, Antigens, Differentiation, B-Lymphocyte, B-Lymphocytes, Humans, Immunoglobulin A, Immunoglobulin A, Secretory, Immunoglobulin D, Immunoglobulin Isotypes, Lymphocyte Activation, Phenotype, Antigens, CD, Transforming Growth Factor beta, Interleukin-10, CD40 Antigens
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