CD19 regulates B cell maturation, proliferation, and positive selection in the FDC zone of murine splenic germinal centers

Immunity. 2005 Jun;22(6):749-61. doi: 10.1016/j.immuni.2005.04.012.

Abstract

Mice with mutations in CD19 Y482/Y513 form germinal centers (GC) but fail to produce high-affinity antibodies. In these mice, GC B cell differentiation, proliferation, and class switching occur but are defective. Altered CD19 signaling results in retention of early GC B cells and reduced proliferation in the follicular dendritic cell (FDC) zone of GC, and causes failure to select for high-affinity mutations. In normal mice, the earliest detectable aggregates of GC B cells are in contact with FDC and IgM+ cells are only found in the FDC zone, further evidence that the FDC zone is the site of initial GC B cell proliferation, differentiation, and class switching. Proliferation in the non-FDC zone and somatic mutation are not dependent on CD19, indicating separate signaling requirements for the two GC compartments, but these CD19-independent GC functions are not sufficient to generate high-affinity antibodies and B cell memory.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD19 / immunology*
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Proliferation*
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Immunohistochemistry
  • Lymphocyte Activation / immunology
  • Mice
  • Microscopy, Fluorescence
  • Polymerase Chain Reaction
  • Somatic Hypermutation, Immunoglobulin / immunology
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Antigens, CD19