MHC-restricted Ig V region-driven T-B lymphocyte collaboration: B cell receptor ligation facilitates switch to IgG production.
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.
Munthe
Ludvig A
LA
Institute of Immunology, Rikshospitalet University Hospital, University of Oslo, N-0027 Oslo, Norway. l.a.munthe@labmed.uio.no
Os
Audun
A
Zangani
Michael
M
Bogen
Bjarne
B
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002450:Cell Communication / Q000276:immunology*; D006649:Histocompatibility Antigens; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell