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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / genetics
  • Antibodies, Anti-Idiotypic / immunology
  • Autoimmune Diseases / metabolism
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Disease Models, Animal
  • Histocompatibility Antigens Class II / metabolism*
  • Immunoglobulin G
  • Mice
  • Mice, Inbred BALB C
  • Neuropeptides / metabolism*
  • Receptors, Antigen, B-Cell / metabolism*
  • T-Lymphocytes / immunology*


  • Antibodies, Anti-Idiotypic
  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Neuropeptides
  • Receptors, Antigen, B-Cell
  • peptide V