title: Actin reorganization is required for the formation of polarized B cell receptor signalosomes in response to both soluble and membrane-associated antigens.
abstract: B cells encounter both soluble Ag (sAg) and membrane-associated Ag (mAg) in the secondary lymphoid tissue, yet how the physical form of Ag modulates B cell activation remains unclear. This study compares actin reorganization and its role in BCR signalosome formation in mAg- and sAg-stimulated B cells. Both mAg and sAg induce F-actin accumulation and actin polymerization at BCR microclusters and at the outer rim of BCR central clusters, but the kinetics and magnitude of F-actin accumulation in mAg-stimulated B cells are greater than those in sAg-stimulated B cells. Accordingly, the actin regulatory factors, cofilin and gelsolin, are recruited to BCR clusters in both mAg- and sAg-stimulated B cells but with different kinetics and patterns of cellular redistribution. Inhibition of actin reorganization by stabilizing F-actin inhibits BCR clustering and tyrosine phosphorylation induced by both forms of Ag. Depolymerization of F-actin leads to unpolarized microclustering of BCRs and tyrosine phosphorylation in BCR microclusters without mAg and sAg, but with much slower kinetics than those induced by Ag. Therefore, actin reorganization, mediated via both polymerization and depolymerization, is required for the formation of BCR signalosomes in response to both mAg and sAg.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Chaohong
authors.initials: C
authors.lastname: Liu
authors.forename: Heather
authors.initials: H
authors.lastname: Miller
authors.forename: Gregory
authors.initials: G
authors.lastname: Orlowski
authors.forename: Haiyin
authors.initials: H
authors.lastname: Hang
authors.forename: Arpita
authors.initials: A
authors.lastname: Upadhyaya
authors.forename: Wenxia
authors.initials: W
authors.lastname: Song
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D051339:Actin Depolymerizing Factors / Q000502:physiology; D000199:Actins / Q000737:chemistry*; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001704:Biopolymers; D002462:Cell Membrane / Q000276:immunology; D016764:Cell Polarity; D003599:Cytoskeleton / Q000648:ultrastructure*; D018260:Gelsolin / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D012995:Solubility
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D000941:Antigens; D001704:Biopolymers; D018260:Gelsolin; D011947:Receptors, Antigen, B-Cell