CD19 regulates B cell maturation, proliferation, and positive selection in the FDC zone of murine splenic germinal centers.
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.
Wang
Yue
Y
Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Carter
Robert H
RH
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D018941:Antigens, CD19