CXCR5-deficient mice develop functional germinal centers in the splenic T cell zone.
The chemokine receptor CXCR5 is thought to be essential for the migration of B cells into the network of follicular dendritic cells in the spleen. However, as shown here, B cells and follicular dendritic cells do co-localize, albeit aberrantly, even in the absence of CXCR5. In mice lacking CXCR5 both cell types are found in a broad ring around the sinuses of the marginal zones. Upon immunization with the T cell-dependent antigen 2-phenyl-oxazolone, ectopic germinal centers develop in the periarteriolar lymphocyte sheath. A network of follicular dendritic cells forms in the vicinity of the central arteriole within which the antigen-activated B cells proliferate. The analysis of the expressed V gene repertoire revealed that during B cell proliferation, hypermutation is activated and V region genes accumulate somatic mutations. The pattern of somatic mutations suggests that affinity selection may occur. This analysis confirms that in CXCR5-deficient mice, the organization of splenic primary follicles is severely impaired. However, within the T cell zone a micro-environment is built up, which provides all requirements needed for the affinity maturation to take place.
Voigt
I
I
Deutsches Rheuma Forschungs-Zentrum, Berlin, Germany.
Camacho
S A
SA
de Boer
B A
BA
Lipp
M
M
Förster
R
R
Berek
C
C
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
C513179:CXCR5 protein, mouse; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine