Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A.

Abstract

SummaryIn the present report, we have investigated the in vitro differentiation of surface(s) slgD + and slgD-human B cells into Ig-secreting calls in response to various stimuli, slgD + 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 slgD expression were highly enriched for naive B lymphocytes. Conversely, slgD-B cells expressed some of the antigens spedfically associated with germinal center B cells. T cell-independent differentiation of slgD + 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'yPdI (CDw32 L cells). In this experimental system, sIgD + B cells were exclusively proned for IgM synthesis, whereas sIgD-B ceils produced IgG, IgM, and IgA. Both the human and viral forms of interleukin 10 (ILd0) strongly increased the Ig secretion by sIgD + and slgD-B cells simultaneously activated through slgs and CD40. IgM and IgG constituted the predominant Ig isotype produced by slgD + and slgD-B cells, respectively, in response to IL-10. slgD + B cells could be induced for IgA synthesis upon co-culturing with transforming growth factor (TGF-~) and II.-10, in the presence of an anti-CD40 monodonal antibody presented by the CDw32 L cells. In contrast, TGF-~ suppressed the IL-10-mediated IgG, IgM, and IgA secretions by slgD-B cells, slgD + B cells could not be induced for IgA synthesis by TGF-~ and Ibl0 after crosslinking of their slgs, 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-B 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-B is involved in the regulation of IgA isotype selection in humans.

Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

“…It is more likely that the pro-inflammatory microenvironment generated by excess LPS in the NOMV interferes with the development of mucosal IgA plasma cells. B cell switching to the IgA isotype has been linked with a number of key cytokines such as IL-10 and TGF-b [22]. In addition, T helper polarisation has been described as dependent on the antagonist effects of IL-12 and IFN-c (Th1-skewing) and of IL-10 and IL-4 (Th2-skewing) [23].…”

Autoantibodies in Diabetes

“…Other regulatory factors are the antigen dose (99), the strength of T-cell receptor binding by the antigen-major histocompatibility complex (100), and the type of antigen-presenting cell interacting with a T-cell (101). IgG4 and IgE are selected in the presence of interleukin (IL)-4 and IL-13 (102,103), whereas IgG1 and IgG3 require the presence of IL-10 (104,105), and IgA needs the combined presence of IL-10 and transforming growth factor-␤ (106,107).…”

1,25‐dihydroxyvitamin D3 promotes IL‐10 production in human B cells

“…B cells are promoted to differentiate into plasmablasts by IL-10, and their antibody class switch to IgA, IgG and IgM is augmented [14,15], while B cell migration and expression of the pro-inflammatory cytokine IL-6 is inhibited [14,16]. IL-10 can be expressed by many different cell types, including gut endothelial cells, dendritic cells, monocytes, and T and B lymphocytes [14].…”