International Immunology Advance Access originally published online on April 11, 2005
International Immunology 2005 17(5):581-589; doi:10.1093/intimm/dxh241
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Two waves of memory B-cell generation in the primary immune response
1 Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
2 Division of Immunobiology, Research Institute for Biological Science and 5 Genome and Drug Research Center, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan
3 Division of Infectious Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan
4 Department of Developmental Genetics (H2) Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Correspondence to: T. Takemori; E-mail: ttoshi{at}nih.go.jp
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 IgVH 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.
Keywords: affinity maturation, blocking antibody, germinal center, ICOS, somatic mutations
Transmitting editor: T. Watanabe
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