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

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• 作者：Azahara-Marí ; a Garcí ; a-Serna^a ; ^b ; ¹ ; Marí ; a-José ; Alcaraz-Garcí ; a^a ; ^b ; ¹ ; Natalia Ruiz-Lafuente^a ; ^b ; Silvia Sebastiá ; n-Ruiz^a ; ^b ; Carlos-Manuel Martí ; nez^a ; ^c ; Marí ; a-Rosa Moya-Quiles^a ; ^b ; Alfredo Minguela^a ; ^b ; Ana-Marí ; a Garcí ; a-Alonso^a ; ^b ; Elena Martí ; n-Orozco^a ; ^d ; Antonio Parrado^a ; ^b ; ^{antonio.parrado@carm.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ANOVA ; analysis of variance ; BCR ; B-cell receptor ; BM ; bone marrow ; CM ; complete medium ; DN ; double negative ; DP ; double positive ; FO ; follicular ; GC ; germinal center ; GEF ; guanine nucleotide exchange factor ; GEP ; gene expression profile ; IB ; isolation buffer ; LF ; lymphoid follicle ; MZ ; marginal zone ; NK ; natural killer ; PB ; peripheral blood ; qPCR ; quantitative PCR ; SP ; single positive
• 刊名：Immunobiology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：221
• 期：12
• 页码：1343-1350
• 全文大小：1459 K

文摘

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.