SIGNALING VIA MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES AND ANTIGEN RECEPTORS ENHANCES THE B-CELL RESPONSE TO GP39/CD40 LIGAND
SIGNALING VIA MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES AND ANTIGEN RECEPTORS ENHANCES THE B-CELL RESPONSE TO GP39/CD40 LIGAND
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DOI：
10.1002/eji.1830250515
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发表时间：
1995-05-01
影响因子：
5.4
通讯作者：
BERTON, MT
中科院分区：
文献类型：
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作者：
BISHOP, GA;WARREN, WD;BERTON, MT
激活的T细胞通过其CD40分子和淋巴因子受体在体外诱导静息B细胞的增殖和分化。然而，尽管B细胞表达CD40和淋巴因子受体，但在体内很少观察到被激活的T细胞激活的广泛的非特异性多克隆B细胞。本研究旨在验证一种假设，即通过B细胞抗原(Ag)受体(膜免疫球蛋白，MiG)和主要组织相容性复合体(MHC)II类分子传递的信号增强了B细胞对CD40介导的信号的反应性，从而提供了对Ag非特异性、MHC非限制性CD40信号的特异性。为了验证这一假设，将抗原特异的小鼠B细胞克隆CH12.LX和新鲜分离的静息B细胞与可溶性或膜结合形式的CD40 T细胞配体(CD40L)一起培养，在存在或不存在由Ag或抗IgM、白介素4和II类特异性单抗(MAb)提供的额外信号的情况下进行培养。MiG介导的信号可显著促进CH12.LX细胞的分化和脾B细胞对两种形式CD40L的反应，其中以在接受其他信号之前先用Ag培养细胞的促进作用最强。CD40L对CD40L的反应通过与II类特异性单抗同时培养而不是I类特异性单抗同时培养而进一步增强。限制CD40L浓度时，增强作用最强。第二类MHC介导的信号能够增强抗原特异性B细胞对CD40介导的信号的反应性，这可能选择性地促进能够与辅助T细胞同源相互作用的B细胞克隆的激活。
Activated T cells induce proliferation and differentiation of resting B cells in vitro through their CD40 molecules and lymphokine receptors. However, despite constitutive B cell expression of CD40 and lymphokine receptors, widespread nonspecific polyclonal B cell activation by activated T cells is seldom observed in vivo. The present study was designed to test the hypothesis that signals delivered via the B cell antigen (Ag) receptor (membrane immunoglobulin, mIg) and major histocompatibility complex (MHC) class II molecules enhance B cell responsiveness to CD40-mediated signals, providing specificity to the Ag-nonspecific, MHC-unrestricted CD40 signal. To test this hypothesis, both an Ag-specific mouse B cell clone CH12.LX, and freshly isolated resting splenic B cells were cultured with either soluble or membrane-bound forms of the T cell ligand for CD40 (CD40L), in the presence or absence of additional signals provided by Ag or anti-IgM, interleukin-4, and class II-specific monoclonal antibody (mAb). Differentiation of CH12.LX cells and proliferation of splenic B cells in response to both forms of CD40L was greatly enhanced by exposure to mig-mediated signals, with greatest enhancement seen when cells were cultured with Ag prior to receiving other signals. Response to CD40L was further enhanced by concurrent culture with class II-specific, but not class I-specific mAb. Enhancement was greatest at limiting concentrations of CD40L. The ability of class II MHC-mediated signals to enhance Ag-specific B cell responsiveness to CD40-mediated signaling may selectively promote the activation of B cell clones capable of cognate interactions with helper T cells.