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Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25850-25859. doi: 10.1073/pnas.1902836116. Epub 2019 Dec 3.

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

Author information

1
Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway; peter.csaba.huszthy@rr-research.no bjarne.bogen@medisin.uio.no.
2
Department of Immunology, Oslo University Hospital, 0424 Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
4
Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY 10065.
5
Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305.
6
Department of Biosciences, University of Oslo, N-0316 Oslo, Norway.
7
Nextera AS, N-0349 Oslo, Norway.
8
KG Jebsen Centre for Research on Influenza Vaccines, Institute of Clinical Medicine, University of Oslo, N-0316 Oslo, Norway.
9
Institute of Oral Biology, Faculty of Dentistry, University of Oslo, N-0316 Oslo, Norway.
10
KG Jebsen Centre for B cell malignancies, Institute of Clinical Medicine, University of Oslo, N-0316 Oslo, Norway.

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.

KEYWORDS:

BCR ligation by antigen; M315-like BCR; V-gene modified mouse model; idiotype-driven T–B collaboration; idiotypic peptide: MHCII

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