Parameters governing exhaustion of rare T cell-independent neutralizing IgM-producing B cells after LCMV infection

Eur J Immunol. 2006 Dec;36(12):3175-85. doi: 10.1002/eji.200636087.


The late appearance of neutralizing antibodies (nAb) against lymphocytic choriomeningitis virus (LCMV) has been attributed to various factors including immunopathology, low frequency of high-affinity specific B cells and competition by nonspecific polyclonal B cell activation. To investigate the activation of LCMV-nAb-producing B cells early following infection, we performed adoptive transfers of LCMV-specific B cells into WT recipients. By modulating parameters such as viral load, number of specific B cells and presence of T cell help, we found that a high antigen-to-B cell ratio led to normal IgM responses. IgG and memory response however, were impaired as most nAb-producing B cells rapidly terminally differentiated into short-lived IgM plasma cells. Lowering the antigen-to-B cell ratio, or increasing the level of T cell help, could rescue the class-switched antibody response. Upon infection, a low frequency of LCMV-nAb-producing B cells, as observed in WT mice, results in a high antigen-to-B cell ratio and is likely to lead to terminal differentiation - and elimination - of these rare B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Immunoglobulin Class Switching / physiology
  • Immunoglobulin Isotypes / biosynthesis
  • Immunoglobulin M / biosynthesis*
  • Immunoglobulin M / physiology
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neutralization Tests
  • Rats
  • T-Lymphocytes, Helper-Inducer / immunology


  • Immunoglobulin Isotypes
  • Immunoglobulin M