Two waves of memory B-cell generation in the primary immune response

Int Immunol. 2005 May;17(5):581-9. doi: 10.1093/intimm/dxh241. Epub 2005 Apr 11.

Abstract

Memory B cells can be generated independently of germinal center (GC) formation and affinity maturation in Bcl-6-deficient mice, but the contribution of the GC-independent pathway for memory B-cell generation in normal mice remains unknown. To examine this, we administrated anti-inducible co-stimulator (ICOS) mAbs into mice at the onset of GC formation in the primary response. This manipulation affected the generation of GC B cells in the spleen, but neither IgG1 memory B cell nor production of IgG1 long-term antibody was affected. In ICOS-manipulated mice, GC B cells accumulated somatic mutations in the IgV(H) genes and underwent affinity maturation; however, memory B cells scarcely accumulated mutations and reconstituted the secondary response by low affinity, supporting the notion that low-affinity memory B cells are generated in a GC-independent manner. Thus, it appears that memory B cells are established by two different pathways, associated with or without GC reaction and affinity maturation. The generation and long-term persistence of low-affinity IgG1 memory B cells and antibodies in ICOS-manipulated mice support the idea that low-affinity memory B cells may give rise to long-term antibody-forming cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • B-Lymphocytes / immunology*
  • Female
  • Germinal Center / immunology*
  • Immunization
  • Immunoglobulin G / immunology
  • Immunologic Memory / immunology*
  • Inducible T-Cell Co-Stimulator Protein
  • Mice
  • Mice, Inbred C57BL
  • Spleen / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Icos protein, mouse
  • Immunoglobulin G
  • Inducible T-Cell Co-Stimulator Protein