title: T-cell-independent immune responses do not require CXC ligand 13-mediated B1 cell migration.
abstract: The dynamic movement of B cells increases the probability of encountering specific antigen and facilitates cell-cell interactions required for mounting a rapid antibody response. B1a and B1b cells are enriched in the coelomic cavity, contribute to T-cell-independent (TI) antibody responses, and increase in number upon antigen exposure. B1 cell movement is largely governed by Cxc ligand 13 (Cxcl13), and mice deficient in this chemokine have a severe reduction in peritoneal B1 cells. In this study, we examined the role of Cxcl13-dependent B cell migration using Borrelia hermsii infection or intraperitoneal immunization with pneumococcal polysaccharide or 4-hydroxy-3-nitrophenyl-acetyl (NP)-Ficoll, all of which induce robust antibody responses from B1b cells. Surprisingly, we found that antibody responses to B. hermsii or to FhbA, an antigenic target of B1b cells, and the resolution of bacteremia were indistinguishable between wild-type and Cxcl13-/- mice. Importantly, we did not observe an expansion of peritoneal B1b cell numbers in Cxcl13-/- mice. Nonetheless, mice that had resolved infection were resistant to reinfection, indicating that the peritoneal B1b cell reservoir is not required for controlling B. hermsii. Furthermore, despite a reduced peritoneal B1b compartment, immunization with pneumococcal polysaccharide vaccine yielded comparable antigen-specific antibody responses in wild-type and Cxcl13-/- mice and conferred protection against Streptococcus pneumoniae. Likewise, immunization with NP-Ficoll elicited similar antibody responses in wild-type and Cxcl13-/- mice. These data demonstrate that homing of B1 cells into the coelomic cavity is not a requirement for generating protective TI antibody responses, even when antigen is initially localized to this anatomical compartment.
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, 233 South 10th Street, BLSB 726, Philadelphia, PA 19107, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Colombo
authors.forename: Guizhi
authors.initials: G
authors.lastname: Sun
authors.forename: Kishore R
authors.initials: KR
authors.lastname: Alugupalli
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001402:B-Lymphocytes / Q000502:physiology*; D016470:Bacteremia / Q000276:immunology; D001899:Borrelia Infections / Q000276:immunology; D002465:Cell Movement; D054382:Chemokine CXCL13 / Q000502:physiology*; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D022242:Pneumococcal Vaccines / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D007075:Immunoglobulin M; D022242:Pneumococcal Vaccines