B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

Cell Rep. 2018 Nov 6;25(6):1395-1403.e4. doi: 10.1016/j.celrep.2018.10.042.


Antigen-dependent engagement of germinal center (GC) B cell receptors (BCRs) promotes antigen internalization and presentation for follicular helper T cells. However, whether BCR signaling is critical or synergistic with T cell help for GC B cell selection or differentiation is unclear. Here, by adapting an experimental approach that enables independent delivery of BCR-crosslinking antigen or T cell help to GC B cells in vivo, we showed that T cell help was sufficient to induce GC B cell expansion and plasmablast formation. However, although BCR crosslinking could not by itself promote GC B cell selection or differentiation, it could synergize with T cell help to enhance the GC and plasmablast responses when T cell help was limiting. These findings indicate that GC B cells can integrate variable inputs from T cell help and BCR signaling in vivo for an optimal process of selection and differentiation, critical for potent long-term humoral immunity.

Keywords: B cell receptor; B cell selection and differentiation; T cell help; follicular helper T cells; germinal centers; plasma cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Differentiation
  • Cross-Linking Reagents / metabolism*
  • Female
  • Germinal Center / cytology
  • Germinal Center / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Plasma Cells / cytology
  • Plasma Cells / metabolism
  • Receptors, Antigen, B-Cell / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / metabolism*


  • Cross-Linking Reagents
  • Receptors, Antigen, B-Cell