Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire.
In T cell-dependent immune responses, high-affinity B cells are selected and differentiate into memory cells; however, the mechanism behind this process remains largely unknown. Here, we report that the selection of high-affinity B cells within germinal centers (GCs) is impaired in Fas-deficient lpr mice in the primary response, probably owing to inefficient negative selection. The memory compartment in control mice is mostly established by precursors generated from the early GCs, whereas the lpr defect expands the memory compartment by the increased recruitment of newly generated precursors from the late GCs, resulting in the accumulation of heavily mutated memory B cells at high frequency. These results suggest that Fas is required for clonal selection within GCs and the establishment of the memory B cell repertoire.
Takahashi
Y
Y
Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, 162-8640, Tokyo, Japan.
Ohta
H
H
Takemori
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007156:Immunologic Memory; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D009154:Mutation; D009244:NAD+ Nucleosidase / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D017931:DNA Primers; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D008562:Membrane Glycoproteins; D019014:fas Receptor; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1