High affinity IgM(+) memory B cells are generated through a germinal center-dependent pathway.

Academic Article

Abstract

  • During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM(+) memory cells and that this process continues even after CSR is accomplished.
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    Keywords

  • Affinity maturation, Class switch recombination, Germinal center reaction, IgM, Somatic hypermutation, Animals, Antibody Affinity, B-Lymphocyte Subsets, B-Lymphocytes, Base Sequence, Cell Differentiation, Cell Separation, Female, Flow Cytometry, Germinal Center, Immunoglobulin Class Switching, Immunoglobulin M, Immunologic Memory, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Polymerase Chain Reaction, Somatic Hypermutation, Immunoglobulin
  • Digital Object Identifier (doi)

    Author List

  • Hara Y; Tashiro Y; Murakami A; Nishimura M; Shimizu T; Kubo M; Burrows PD; Azuma T
  • Start Page

  • 617
  • End Page

  • 627
  • Volume

  • 68
  • Issue

  • 2 Pt C