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EBI2 mediates B cell segregation between the outer and centre follicle.

Nature | Aug 27, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19597478

B cell follicles are specialized microenvironments that support events necessary for humoral immunity. After antigen encounter, activated B cells initially seek T-cell help at the follicle-T-zone boundary and then move to interfollicular and T-zone distal (outer) regions of the follicle. Subsequently, some cells move to the follicle centre, become germinal centre B cells and undergo antibody affinity maturation. Although germinal centres within follicles were described in 1885 (ref. 12), the molecular cues mediating segregation of B cells between the outer and centre follicle have remained undefined. Here we present a role for the orphan G-protein-coupled receptor, Epstein-Barr virus induced molecule-2 (EBI2, also known as GPR183), in this process. EBI2 is expressed in mature B cells and increases in expression early after activation, before being downregulated in germinal centre B cells. EBI2 deficiency in mice led to a reduction in the early antibody response to a T-dependent antigen. EBI2-deficient B cells failed to move to the outer follicle at day 2 of activation, and instead were found in the follicle centre, whereas EBI2 overexpression was sufficient to promote B cell localization to the outer follicle. In mixed bone marrow chimaeras, EBI2-deficient B cells phenocopied germinal centre B cells in preferentially localizing to the follicle centre. When downregulation of EBI2 in wild-type B cells was antagonized, participation in the germinal centre reaction was impaired. These studies identify an important role for EBI2 in promoting B cell localization in the outer follicle, and show that differential expression of this receptor helps position B cells appropriately for mounting T-dependent antibody responses.

Pubmed ID: 19597478 RIS Download

Mesh terms: Animals | B-Lymphocytes | Chemokine CXCL13 | Gene Expression Regulation | Germinal Center | Lymphocyte Activation | Mice | Mice, Inbred C57BL | Receptors, G-Protein-Coupled

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Associated grants

  • Agency: NIAID NIH HHS, Id: R01 AI045073
  • Agency: NIAID NIH HHS, Id: R01 AI045073-09
  • Agency: NIAID NIH HHS, Id: R01 AI045073-10
  • Agency: NIAID NIH HHS, Id: R01 AI045073-11
  • Agency: NIAID NIH HHS, Id: R37 AI040098
  • Agency: NIAID NIH HHS, Id: R37 AI040098-11
  • Agency: NIAID NIH HHS, Id: R37 AI040098-12
  • Agency: NIAID NIH HHS, Id: R37 AI040098-13
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

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