IgG-Immune Complexes Promote B Cell Memory by Inducing BAFF

J Immunol. 2016 Jan 1;196(1):196-206. doi: 10.4049/jimmunol.1402527. Epub 2015 Nov 30.


Memory B cell responses are vital for protection against infections but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high-affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG-immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent Ag leads to IC-FcγR interactions that induce dendritic cells to secrete BAFF, which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary Ab responses. BAFF also contributed to the maintenance and/or expansion of the follicular helper T cell population, although it was dispensable for their formation. Thus, early Ab responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen-Antibody Complex / immunology*
  • B-Cell Activating Factor / biosynthesis*
  • B-Cell Activating Factor / genetics
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Immunoglobulin G / immunology*
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins c-bcl-6 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology


  • Antigen-Antibody Complex
  • B-Cell Activating Factor
  • Fcgr3 protein, mouse
  • Immunoglobulin G
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, IgG
  • Tnfsf13b protein, mouse