title: The actin-bundling protein L-plastin is essential for marginal zone B cell development.
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. In this article, we demonstrate the requirement for the actin-bundling protein L-plastin (LPL) in B cell motility toward the chemokines CXCL12 and CXCL13 and the lipid chemoattractant sphingosine-1-phosphate, which guide normal B cell development. Impaired motility of B cells in LPL(-/-) mice correlated with diminished splenic maturation of B cells, with a moderate (40%) loss of follicular B cells and a profound (>80%) loss of marginal zone B cells. Entry of LPL(-/-) B cells into the lymph nodes and bone marrow of mice 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 may participate 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 diminished in LPL(-/-) B cells stimulated with chemokine. Finally, a well-characterized role of marginal zone B cells is the generation of a rapid humoral response to polysaccharide Ags. LPL(-/-) mice exhibited a defective Ab response to Streptococcus pneumoniae, indicating a functional consequence of defective marginal zone B cell development in LPL(-/-) mice.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Todd
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Deady
authors.forename: Sharon Celeste
authors.initials: SC
authors.lastname: Morley
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003598:Cytoskeletal Proteins; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000276:immunology* / Q000378:metabolism; D013154:Spleen
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C066559:Lcp1 protein, mouse