MHC-restricted Ig V region-driven T-B lymphocyte collaboration: B cell receptor ligation facilitates switch to IgG production |
| |
Authors: | Munthe Ludvig A Os Audun Zangani Michael Bogen Bjarne |
| |
Affiliation: | Institute of Immunology, Rikshospitalet University Hospital, University of Oslo, N-0027 Oslo, Norway. l.a.munthe@labmed.uio.no |
| |
Abstract: | B cells spontaneously process their endogenous Ig and present V region peptides on their MHC class II molecules. We have here investigated whether B cells collaborate with V region-specific CD4+ T cells in vivo. By use of paired Ig L chain-transgenic and TCR-transgenic mice and cell transfer into normal hosts, we demonstrate that B cell presentation of a V(L) region peptide to CD4+ T cells results in germinal centers, plasma cells, and Ab secretion. Because the transgenic B cells have a fixed L chain but polyclonal H chains, their B cell receptor (BCR) repertoire is diverse and may bind a multitude of ligands. In a hapten-based system, BCR ligation concomitant with V region-driven T-B collaboration induced germinal center formation and an IgM --> IgG isotype switch. In the absence of BCR ligation, mainly IgM was produced. Consistent with this, prolonged V region-driven T-B collaboration resulted in high titers of IgG autoantibodies against ubiquitous self-Ags, while natural-type Abs against exotic bacteria remained IgM. Taken together, V region-driven T-B collaboration may explain induction of natural IgM Abs (absence of BCR ligation) and IgG autoantibodies (BCR ligation by autoantigen) and may be involved in the development of autoimmunity. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|