Mzb1 protein regulates antibody secretion and integrin activation in innate-like B cells
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1
Max Planck Institute of Immunobiology and Epigenetics, Department of Cellular and Molecular Immunology, Germany
Marginal zone (MZ) B cells of the spleen and B1 cells, termed innate-like B cells, differ from Follicular B cells by their attenuated Ca2+ mobilization, fast antibody secretion, and increased cell adhesion. We identified and characterized Mzb1 as an endoplasmic reticulum (ER)-localized and B cell-specific protein that is most abundantly expressed in innate-like B cells. Knockdown of Mzb1 in MZ B cells increased Ca2+ mobilization and reduced integrin-mediated cell adhesion. To gain further insight into the function of Mzb1 in vivo and to study its role in the humoral immune response, we have generated and analyzed Mzb1 knock out mice. To assess the function of Mzb1 in the initiation of an early response to blood-borne T-cell-independent type 2 (TI-2) antigens, we intravenously challenged Mzb1+/+ and Mzb1-/- mice with the TI-2 antigen TNP-Ficoll or Streptococcus pneumonia type 3 polysaccharide (S.p. PS). The immune response of Mzb1-/- mice was significantly reduced compared with Mzb1+/+ mice. We also detected in Mzb1-/- mice, reduced amounts of anti-TNP-specific antibodies of the IgG3 isotype, consistent with the role of MZ B cell in the generation of IgG3 in a TI-2 response. We could also demonstrate a reduced integrin activation and reduced adhesion capacity to the molecules ICAM1 and VCAM1, in Mzb1-/- MZ B cells compared to Mzb1 expressing wild type MZ B Cells. Together, these results suggest that the ER protein Mzb1, is important for immunoglobulin secretion and integrin-mediated adhesion.
Keywords:
Marginal zone B cells,
Immunoglobulins,
Integrins,
Adhesion,
Endoplasmic Reticulum
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Innate Immunity
Citation:
Andreani
V,
Rosenbaum
M,
Kapoor
T and
Grosschedl
R
(2015). Mzb1 protein regulates antibody secretion and integrin activation in innate-like B cells.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00035
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Received:
14 Apr 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
Dr. Virginia Andreani, Max Planck Institute of Immunobiology and Epigenetics, Department of Cellular and Molecular Immunology, Freiburg, Freiburg, D-79108, Germany, virandreani@gmail.com