B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells

Author:

Huszthy Peter CsabaORCID,Gopalakrishnan Ramakrishna Prabhu,Jacobsen Johanne Tracey,Haabeth Ole Audun WernerORCID,Løset Geir ÅgeORCID,Braathen Ranveig,Schenck Karl,Tveita Anders AuneORCID,Munthe Ludvig Andre,Bogen Bjarne

Abstract

The B cell receptors (BCRs) for antigen express variable (V) regions that are enormously diverse, thus serving as markers on individual B cells. V region-derived idiotypic (Id) peptides can be displayed as pId:MHCII complexes on B cells for recognition by CD4+T cells. It is not known if naive B cells spontaneously display pId:MHCII in vivo or if BCR ligation is required for expression, thereby enabling collaboration between Id+B cells and Id-specific T cells. Here, using a mouse model, we show that naive B cells do not express readily detectable levels of pId:MHCII. However, BCR ligation by Ag dramatically increases physical display of pId:MHCII, leading to activation of Id-specific CD4+T cells, extrafollicular T–B cell collaboration and some germinal center formation, and production of Id+IgG. Besides having implications for immune regulation, the results may explain how persistent activation of self-reactive B cells induces the development of autoimmune diseases and B cell lymphomas.

Funder

Norges Forskningsråd

Ministry of Health and Care Services | Helse Sør-Øst RHF

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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