Damle N K, Linsley P S, Ledbetter J A
Oncogen Division, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Eur J Immunol. 1991 May;21(5):1277-82. doi: 10.1002/eji.1830210527.
Cognate interactions between major histocompatibility complex class II antigen (Ag)-reactive CD4+ T helper (Th) and Ag-presenting B cells induce first the activation of B cells and their subsequent differentiation into Ig-secreting cells (IgSC). The Th cell-associated homodimeric glycoprotein CD28 has been implicated as an important regulator of Th activation. Recently, B cell-associated early activation Ag B7 has been identified as a ligand for the CD28 molecule. In this study, we have examined using monoclonal antibodies (mAb) the roles of CD28 and B7 molecules during the Th-B cell cognate interactions leading to the differentiation of B7+ B cells. Anti-CD28 mAb 9.3 specifically inhibited proliferative responses of CD4+ T cells to both allogeneic B cells and soluble Ag-presenting autologous non-T cells. In addition, anti-CD28 mAb 9.3 inhibited Th-induced differentiation of alloantigen-presenting B cells into ISC. Similar inhibition of both Ag-induced Th activation and B cell differentiation into ISC was observed using mAb BB1 which recognizes a B cell-associated molecule B7. In contrast, non-cognate Th-independent exogenous interleukin 6-induced differentiation of B7+ B cells into ISC was not inhibited by mAb to either molecule. These results clearly demonstrate the involvement of CD28 on Th and its ligand B7 on B cells during cognate Th-B interactions leading to the differentiation of B cells. Furthermore, these results also suggest the development of new mAb-based therapeutic approaches for exaggerated B cell activation associated with certain autoimmune diseases such as systemic lupus erythematosus.
主要组织相容性复合体II类抗原（Ag）反应性CD4 + T辅助（Th）细胞与抗原呈递B细胞之间的同源相互作用首先诱导B细胞活化，随后使其分化为分泌免疫球蛋白的细胞（IgSC）。Th细胞相关的同型二聚体糖蛋白CD28被认为是Th细胞活化的重要调节因子。最近，B细胞相关的早期活化抗原B7已被鉴定为CD28分子的配体。在本研究中，我们使用单克隆抗体（mAb）研究了CD28和B7分子在导致B7 + B细胞分化的Th - B细胞同源相互作用中的作用。抗CD28单克隆抗体9.3特异性抑制CD4 + T细胞对同种异体B细胞和可溶性抗原呈递自体非T细胞的增殖反应。此外，抗CD28单克隆抗体9.3抑制Th诱导的同种异体抗原呈递B细胞向ISC的分化。使用识别B细胞相关分子B7的单克隆抗体BB1观察到对Ag诱导的Th活化和B细胞向ISC分化的类似抑制。相比之下，非同源的Th非依赖性外源性白细胞介素6诱导的B7 + B细胞向ISC的分化不受针对这两种分子的单克隆抗体的抑制。这些结果清楚地证明了在导致B细胞分化的同源Th - B相互作用过程中，Th细胞上的CD28及其配体B细胞上的B7的参与。此外，这些结果还提示了基于单克隆抗体的新治疗方法的开发，用于治疗与某些自身免疫性疾病如系统性红斑狼疮相关的过度B细胞活化。
