The actin-bundling protein L-plastin is required for marginal zone B cell development (112.4)

Abstract

Abstract B cell development is exquisitely sensitive to location within specialized niches in the bone marrow and spleen. Location within these niches is carefully orchestrated through chemotactic and adhesive cues. Here we demonstrate the requirement for the actin-bundling protein L-plastin (LPL) in B cell motility towards the chemokines CXCL12 and CXCL13, chemokines that guide normal B cell development. Impaired motility of B cells in LPL-/- mice correlated with diminished splenic maturation of B cells, with a profound (>80%) loss of marginal zone B cells. Entry of LPL-/- B cells into lymph nodes and bone marrow was also impaired. Furthermore, LPL was required for the integrin-mediated enhancement of transwell migration but was dispensable for integrin-mediated lymphocyte adhesion. These results suggest that LPL participates in signaling that enables lymphocyte transmigration. In support of this hypothesis, the phosphorylation of Pyk-2, a tyrosine kinase that integrates chemotactic and adhesive cues, is diminshed in LPL-/- B cells. Furthermore, a well-characterized role of marginal zone B cells is the generation of a rapid humoral response to polysaccharide antigens. LPL-/- mice exhibited a defective antibody response to Streptococcus pneumoniae, and LPL-/- mice succumb rapidly to intra-tracheal infection with Streptococcus pneumoniae. LPL is thus critical for effective immunity against a significant human pathogen.