SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation.
Germinal centers (GCs) are lymphoid tissue structures central to the generation of long-lived, high-affinity, antibody-forming B cells. However, induction, maintenance, and regulation of GCs are not sufficiently understood. The F-actin-binding, Rac-interacting protein SWAP-70 is strongly expressed in activated B cells like those in B follicles. Recent work suggests that SWAP-70 is involved in B-cell activation, migration, and homing. Therefore, we investigated the role of SWAP-70 in the T-dependent immune response, in GC formation, and in differentiation into plasma and memory B cells. Compared with wt, sheep red blood cell (SRBC)-, or NP-KLH-immunized SWAP-70(-/-) mice have strongly reduced numbers of GCs and GC-specific B cells. However, SWAP-70(-/-) NP-specific B cells accumulate outside of the B follicles, and SWAP-70(-/-) mice show more plasma cells in the red pulp and in the bone marrow, and increased NP-specific Ig and antibody-forming B cells. Yet the memory response is impaired. Thus, SWAP-70 deficiency uncouples GC formation from T-dependent antibody and long-lived plasma cell production and causes extrafollicular generation of high-affinity plasma cells, but does not adequately support the memory response.
Quemeneur
Laurence
L
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Angeli
Veronique
V
Chopin
Michael
M
Jessberger
Rolf
R
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization; D007136:Immunoglobulins / Q000276:immunology; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000172:deficiency* / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology*; D012756:Sheep; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D007136:Immunoglobulins; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C113365:Swap70 protein, mouse; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin