Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5.
Germinal center (GC) dark and light zones segregate cells undergoing somatic hypermutation and antigen-driven selection, respectively, yet the factors guiding this organization are unknown. We report here that GC organization was absent from mice deficient in the chemokine receptor CXCR4. Centroblasts had high expression of CXCR4 and GC B cells migrated toward the CXCR4 ligand SDF-1 (CXCL12), which was more abundant in the dark zone than in the light zone. CXCR4-deficient cells were excluded from the dark zone in the context of a wild-type GC. These findings establish that GC organization depends on sorting of centroblasts by CXCR4 into the dark zone. In contrast, CXCR5 helped direct cells to the light zone and deficiency in CXCL13 was associated with aberrant light zone localization.
Allen
Christopher D C
CD
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California 94143-0414, USA.
Ansel
K Mark
KM
Low
Caroline
C
Lesley
Robin
R
Tamamura
Hirokazu
H
Fujii
Nobutaka
N
Cyster
Jason G
JG
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D042282:Microdissection; D011828:Radiation Chimera; D051381:Rats; D019718:Receptors, CXCR4 / Q000276:immunology* / Q000378:metabolism; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C513179:CXCR5 protein, mouse; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C486386:Cxcl13 protein, mouse; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine