The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity.
The chemokine receptor CXCR4 is expressed in B cells at multiple stages of their development. CXCR4 function in humoral immunity has not been fully investigated. We have generated gene-targeted mice in which CXCR4 can be selectively inactivated in B cells and have shown that it is required for retention of B cell precursors in the bone marrow. CXCR4-deficient B cell precursors that migrated prematurely became localized in splenic follicles despite their unresponsiveness to CXCL13. Concomitantly, mature B cell populations were reduced in the splenic marginal zone and primary follicles, and in the peritoneal cavity in the mutant animals, as were T-independent antibody responses. In addition, aberrant B cell follicles formed ectopically in intestinal lamina propria around Peyer's patches. These findings establish an important role for CXCR4 in regulating homeostasis of B cell compartmentalization and humoral immunity.
Nie
Yuchun
Y
Dept. of Microbiology, Columbia University, 701 West 168th St., HHSC 1406, New York, NY 10032, USA.
Waite
Janelle
J
Brewer
Faraha
F
Sunshine
Mary-Jean
MJ
Littman
Dan R
DR
Zou
Yong-Rui
YR
D000818:Animals; D017304:Annexin A5; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D015139:Blotting, Southern; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D010581:Peyer's Patches / Q000276:immunology; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D017304:Annexin A5; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D017931:DNA Primers; D019718:Receptors, CXCR4