Abstract
SummaryB cell responses are regulated by antigen acquisition, processing, and presentation to helper T cells. These functions are thought to depend on contractile activity of non-muscle myosin IIa. Here, we show that B cell-specific deletion of the myosin IIa heavy chain reduced the numbers of bone marrow B cell precursors and splenic marginal zone, peritoneal B1b, and germinal center B cells. In addition, myosin IIa-deficient follicular B cells acquired an activated phenotype and were less efficient in chemokinesis and extraction of membrane-presented antigens. Moreover, myosin IIa was indispensable for cytokinesis. Consequently, mice with myosin IIa-deficient B cells harbored reduced serum immunoglobulin levels and did not mount robust antibody responses when immunized. Altogether, these data indicate that myosin IIa is a negative regulator of B cell activation but a positive regulator of antigen acquisition from antigen-presenting cells and that myosin IIa is essential for B cell development, proliferation, and antibody responses.
Highlights
B cell activation is initiated when B cells bind antigen via their cell-surface B cell antigen receptors (BCRs)
Many B cells engage antigen bound to antigen-presenting cells (APCs), such as subcapsular macrophages and follicular dendritic cells (FDCs), which display unprocessed antigen bound to complement or Fc receptors on their cell surfaces (Carrasco and Batista, 2007; Gonzalez et al, 2010; Junt et al, 2007; Phan et al, 2007; Qi et al, 2006)
To study the role of myosin IIa in B cells, we crossed Myh9fl/fl mice, in which exon 3 of Myh9 is flanked by LoxP sites (Jacobelli et al, 2010), with Cd79aCre (Mb1Cre) and Fcer2Cre (CD23Cre) mice, resulting in mice in which Myh9 is conditionally deleted from early bone marrow (BM) B cell precursors and more mature splenic transitional B cells, respectively (Hobeika et al, 2006; Kwon et al, 2008)
Summary
B cell activation is initiated when B cells bind antigen via their cell-surface B cell antigen receptors (BCRs). This induces signaling and internalization of BCR-antigen complexes. Many B cells engage antigen bound to antigen-presenting cells (APCs), such as subcapsular macrophages and follicular dendritic cells (FDCs), which display unprocessed antigen bound to complement or Fc receptors on their cell surfaces (Carrasco and Batista, 2007; Gonzalez et al, 2010; Junt et al, 2007; Phan et al, 2007; Qi et al, 2006). In contrast to acquisition of free-floating soluble antigen, capture of membrane-bound antigens from APCs requires B cells to apply force to overcome the membrane tether. It has been hypothesized that non-muscle myosin IIa generates these forces
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