Vasoactive intestinal peptide specifically induces human IgA1 and IgA2 production

Abstract

The effects of vasoactive intestinal peptide (VIP) on human IgA1 and IgA2 production were studied. In unfractionated small resting B cells stimulated with anti-CD40 monoclonal antibody (mAb), VIP induced IgA1 and IgA2 production without affecting the production of IgG1, IgG2, IgG3, IgG4, IgM, or IgE. When small B cells were separated into sIgA1+, sIgA2+, sIgA1- and sIgA2- B cells, anti-CD40 mAb plus VIP induced IgA1 and IgA2 production by surface IgA1- (sIgA1-) and sIgA2- B cells, respectively, while having no effect on sIgA1+ and sIgA2+ B cells. This induction by VIP was specific, since anti-CD40 mAb plus other neuropeptides, i.e., somatostatin or substance P, had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Further, anti-CD40 mAb plus various cytokines, including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, transforming growth factor-beta, low molecular weight B cell growth factor, and interferon-gamma, did not induce IgA1 and IgA2 production by sIgA1- and sIgA2- B cells, respectively. These results indicate that in the presence of anti-CD40 mAb, VIP induces IgA1 and IgA2 production by isotype switching.

Vasoactive intestinal peptide induces S(alpha)/S(mu) switch circular DNA in human B cells.

“…The data of neutralization test at the protein level are in agreement with previous findings of IgA production from IgA Ϫ B cells (15).…”

“…Total mRNA was obtained from cultured B cells (1 ϫ 10 7 cells) using Trizol reagent (Life Technologies, Gaithersburg, MD) (21) and then digested with DNase I (Sigma) to remove contaminating DNA. 2 g of total RNA was reverse-transcribed to cDNA using oligo (dT) 15 (Boehringer-Mannheim Co., Indianapolis, IN) as primer and mouse Moloney leukemia virus reverse transcriptase (Life Technologies).…”

“…Vasoactive intestinal peptide (VIP), 1 a major neuropeptide of the central and peripheral nervous system, has been shown to induce IgA production by human IgA Ϫ B cells (15), fetal B cells, pre-B cells (16), and lamina propria mononuclear cells (17). These finding suggested that VIP might function as a role of switch factor for IgA.…”

TGF-β Receptor Signaling Is Critical for Mucosal IgA Responses

“…Representing the most abundant Ig isotype in humans, an important role of IgA in host protection has long been postulated (2,38). The isotype switch to IgA and its secretion can be induced by TGF-␤-dependent and TGF-␤-independent mechanisms (11)(12)(13)(14)(15)(16)(17)(18)(19). Making use of a mouse model lacking T␤R selectively in B cells (24), the present study shows that the efficient production of Ag-specific mucosal IgA is driven by T␤R signaling (Figs.…”

“…TGF-␤ has also attracted significant attention, since in vitro tests showed that TGF-␤ stimulates the isotype switch to IgA, as well as IgA secretion by LPS-stimulated mIgA Ϫ B cells from Peyer's patches and spleen (11)(12)(13)(14)(15). Remarkably, a TGF-␤-independent mechanism of isotype switch to IgA has been proposed in ϩ murine B cells stimulated with LPS and all-trans-retinoic acid (16,17), as well as in human mIgA1/2 Ϫ B cells coincubated with vasoactive intestinal peptide and anti-CD40 mAb (18,19).…”