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Focal Adhesion Kinase Regulates the Localization and Retention of Pro-B Cells in Bone Marrow Microenvironments

2012; American Association of Immunologists; Volume: 190; Issue: 3 Linguagem: Inglês

10.4049/jimmunol.1202639

1550-6606

Shin‐Young Park, Peter Wolfram, Kimberly J. Canty, Brendan A.C. Harley, César Nombela‐Arrieta, Gregory Pivarnik, John P. Manis, Hilary E. Beggs, Leslie E. Silberstein,

Immunotherapy and Immune Responses

Abstract Progenitor B cells reside in complex bone marrow (BM) microenvironments where they receive signals for growth and maturation. We reported previously that the CXCL12-focal adhesion kinase (FAK)-VLA4 pathway plays an important role in progenitor B cell adhesion and migration. In this study, we have conditionally targeted in B cells FAK, and found that the numbers of progenitor pro-B, pre-B, and immature B cells are reduced by 30–40% in B cell-specific FAK knockout mice. When cultured in methylcellulose with IL-7 ± CXCL12, Fak-deleted pro-B cells yield significantly fewer cells and colonies. Using in situ quantitative imaging cytometry, we establish that in longitudinal femoral BM sections, pro-B cells are preferentially localized in close proximity to the endosteum of the metaphyses and the diaphysis. Fak deletion disrupts the nonrandom distribution of pro-B cells and induces the mobilization of pro-B cells to the periphery in vivo. These effects of Fak deletion on pro-B cell mobilization and localization in BM are amplified under inflammatory stress, that is, after immunization with nitrophenol-conjugated chicken γ-globulin in alum. Collectively, these studies suggest the importance of FAK in regulating pro-B cell homeostasis and maintenance of their spatial distribution in BM niches.