Efficient B cell responses to Borrelia hermsii infection depend on BAFF and BAFFR but not TACI.
T cell-independent antibody responses develop rapidly, within 3 to 4 days, and are critical for preventing blood-borne pathogens from evolving into life-threatening infections. The interaction of BAFF, also known as BLyS, with its receptors BAFFR and TACI on B cells is critical for B cell homeostasis and function. Using a synthetic polysaccharide antigen, it has previously been shown that TACI is critical for T cell-independent antibody responses. To examine the role of BAFFR and TACI in T cell-independent antibody responses to an active infection, we utilized the Borrelia hermsii infection system. In this infection system, T cell-independent responses mediated by the B1b cell subset are critical for controlling bacteremia. We found that B1b cells express BAFFR and TACI and that the surface expression of both receptors is upregulated on B1b cells following exposure to whole B. hermsii cells. Surprisingly, we found that TACI(-/-) mice are not impaired either in specific antibody responses to B. hermsii or in controlling B. hermsii bacteremia. In contrast, TACI-deficient mice immunized with heat-killed type 3 serotype pneumococcus cells are impaired in generating pneumococcal polysaccharide-specific responses and succumb to challenge with live type 3 serotype pneumococcus, indicating that TACI is required for T cell-independent antibody responses to bacterial-associated polysaccharides. Although we have found that TACI is dispensable for controlling B. hermsii infection, mice deficient in BAFFR or BAFF exhibit impairment in B. hermsii-specific IgM responses and clearance of bacteremia. Collectively, these data indicate a disparity in the roles for TACI and BAFFR in primary T cell-independent antibody responses to bacterial pathogens.
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Gregory S
GS
Dickinson
Guizhi
G
Sun
Richard J
RJ
Bram
Kishore R
KR
Alugupalli
D000704:Analysis of Variance; D000818:Animals; D053264:B-Cell Activating Factor / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D053265:B-Cell Activation Factor Receptor / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001898:Borrelia / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008193:Lyme Disease / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053303:Transmembrane Activator and CAML Interactor Protein / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053303:Transmembrane Activator and CAML Interactor Protein