title: Integrin-mediated interactions between B cells and follicular dendritic cells influence germinal center B cell fitness.
abstract: Integrin-ligand interactions between germinal center (GC) B cells and Ag-presenting follicular dendritic cells (FDCs) have been suggested to play central roles during GC responses, but their in vivo requirement has not been directly tested. In this study, we show that, whereas integrins αLβ2 and α4β1 are highly expressed and functional on mouse GC B cells, removal of single integrins or their ligands had little effect on B cell participation in the GC response. Combined β2 integrin deficiency and α4 integrin blockade also did not affect the GC response against a particulate Ag. However, the combined integrin deficiency did cause B cells to be outcompeted in splenic GC responses against a soluble protein Ag and in mesenteric lymph node GC responses against gut-derived Ags. Similar findings were made for β2-deficient B cells in mice lacking VCAM1 on FDCs. The reduced fitness of the GC B cells did not appear to be due to decreased Ag acquisition, proliferation rates, or pAKT levels. In summary, our findings provide evidence that αLβ2 and α4β1 play overlapping and context-dependent roles in supporting interactions with FDCs that can augment the fitness of responding GC B cells. We also find that mouse GC B cells upregulate αvβ3 and adhere to vitronectin and milk-fat globule epidermal growth factor VIII protein. Integrin β3-deficient B cells contributed in a slightly exaggerated manner to GC responses, suggesting this integrin has a regulatory function in GC B cells.
authors.affiliation: Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143;
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Rodda
authors.forename: Oliver
authors.initials: O
authors.lastname: Bannard
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000276:immunology*; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019096:Vitronectin / Q000235:genetics / Q000276:immunology
chemical_list: D039041:Integrin alpha4beta1; D039302:Integrin alphaVbeta3; D019096:Vitronectin
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