Focal adhesion kinase regulates the localization and retention of pro-B cells in bone marrow microenvironments

J Immunol. 2013 Feb 1;190(3):1094-102. doi: 10.4049/jimmunol.1202639. Epub 2012 Dec 21.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / transplantation
  • Bone Marrow / immunology
  • Bone Marrow / ultrastructure*
  • Cells, Cultured / cytology
  • Cells, Cultured / drug effects
  • Cellular Microenvironment
  • Chemokine CXCL12 / physiology
  • Chemotaxis, Leukocyte / physiology
  • Colony-Forming Units Assay
  • Female
  • Focal Adhesion Kinase 1 / deficiency
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / physiology*
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / enzymology*
  • Homeostasis
  • Integrin alpha4beta1 / physiology
  • Interleukin-7 / pharmacology
  • Lymphopenia / etiology
  • Lymphopoiesis / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout


  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Integrin alpha4beta1
  • Interleukin-7
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse