Dock10 regulates CD23 expression and sustains B-cell lymphopoiesis in secondary lymphoid tissue

• Published in: Immunobiology (1979) Vol. 221; no. 12; pp. 1343 - 1350
• Main Authors: García-Serna, Azahara-María, Alcaraz-García, María-José, Ruiz-Lafuente, Natalia, Sebastián-Ruiz, Silvia, Martínez, Carlos-Manuel, Moya-Quiles, María-Rosa, Minguela, Alfredo, García-Alonso, Ana-María, Martín-Orozco, Elena, Parrado, Antonio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.12.2016
• Subjects: Advanced Basic Science; Allergy and Immunology; Animals; B cell; B-Lymphocytes - immunology; CD23; cdc42 GTP-Binding Protein - metabolism; Cdc42 GTPase; Cell Differentiation; Cells, Cultured; Chemokine CCL21 - metabolism; Chemokine CXCL13 - metabolism; Dock10; Fc epsilon receptor II (Fcer2); Germinal Center - immunology; Guanine nucleotide exchange factor (GEF); Guanine Nucleotide Exchange Factors - metabolism; Interleukin-4 - metabolism; Lymphoid Tissue - metabolism; Lymphopoiesis; Mice; Mice, Inbred C57BL; Mice, Knockout; Rac GTPase; rac1 GTP-Binding Protein - metabolism; Receptors, IgE - genetics; Receptors, IgE - metabolism; Transcriptome; Fc epsilon receptor II (Fcer2); Guanine nucleotide exchange factor (GEF); Rac GTPase; quantitative PCR; marginal zone; double negative; FO; DN; BM; peripheral blood; B-cell receptor; DP; follicular; B cell; natural killer; analysis of variance; ANOVA; IB; qPCR; GC; SP; Cdc42 GTPase; isolation buffer; complete medium; Dock10; GEF; CM; germinal center; MZ; bone marrow; BCR; double positive; PB; GEP; guanine nucleotide exchange factor; single positive; gene expression profile; LF; lymphoid follicle; NK; CD23
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2016.07.015

Abstract Dock10, a guanine nucleotide exchange factor for the Rho GTPases Rac1 and Cdc42, affects cell morphology, membrane protrusive activity, and cell movement. Dock10 is prominently expressed in lymphoid tissue and upregulated by IL-4 in B cells. To investigate the physiological role of Dock10, WT mice and Dock10 KO mice were used. KO mice showed decreased numbers of B cells in spleen, both follicular B cells and marginal zone B cells, and in peripheral blood, but not in bone marrow. The antiapoptotic effect of IL-4 in vitro, the migratory response to CXCL13 or CCL21 in vitro, and the whole genome expression profile were intact in spleen B cells from KO mice. CD23, the low-affinity receptor for immunoglobulin E, was overexpressed on follicular B cells from KO mice, suggesting that Dock10 negatively regulates membrane CD23 expression. Negative regulation of CD23 expression by Dock10 could play a role in B cell maturation and function.