Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival

Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):E2915-24. doi: 10.1073/pnas.1218131110. Epub 2013 Jul 11.

Abstract

We describe a unique extracellular matrix (ECM) niche in the spleen, the marginal zone (MZ), characterized by the basement membrane glycoproteins, laminin α5 and agrin, that promotes formation of a specialized population of MZ B lymphocytes that respond rapidly to blood-borne antigens. Mice with reduced laminin α5 expression show reduced MZ B cells and increased numbers of newly formed (NF) transitional B cells that migrate from the bone marrow, without changes in other immune or stromal cell compartments. Transient integrin α6β1-mediated interaction of NF B cells with laminin α5 in the MZ supports the MZ B-cell population, their long-term survival, and antibody response. Data suggest that the unique 3D structure and biochemical composition of the ECM of lymphoid organs impacts on immune cell fate.

Keywords: B-cell development; immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrin / genetics
  • Agrin / immunology
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Bone Marrow / immunology*
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Extracellular Matrix / genetics
  • Extracellular Matrix / immunology*
  • Integrin alpha6beta1 / genetics
  • Integrin alpha6beta1 / immunology
  • Laminin / genetics
  • Laminin / immunology
  • Mice
  • Mice, Knockout
  • Spleen / cytology
  • Spleen / immunology*

Substances

  • Agrin
  • Integrin alpha6beta1
  • Laminin
  • laminin alpha5