Brown D M, Phipps R P
Department of Microbiology and Immunology, University of Rochester, School of Medicine and Dentistry, New York 14642.
Cell Immunol. 1995 Mar;161(1):79-87. doi: 10.1006/cimm.1995.1011.
Prostaglandin E2 (PGE2) is a pleiotropic lipid molecule synthesized by macrophages, follicular dendritic cells, and fibroblasts, inhabitants of the B cell microenvironment. It is a potent regulator of B lymphocyte functions including activation and immunoglobulin class switching. To understand the effects of PGE2 on B lymphocyte function, the features of the putative PGE2 receptor on cells of the B lineage must be delineated. This receptor has not yet been characterized on B lymphocytes. Murine B cell lymphomas were used as a model to evaluate B lineage PGE2 receptors since they elevate intracellular cAMP in response to PGE2. Scatchard analysis indicates that the PGE2 receptor on both CH31 and CH12 exists in a single high-affinity state, with the CH12 B lymphoma possessing three times more receptors per cell compared to CH31. Interestingly, the PGE2 receptor is subject to regulation as a 20-hr LPS treatment increased PGE2 receptor number by two- to threefold on CH12 and CH31 B cell lymphomas, while dissociation constants remained similar. Finally, Scatchard analysis of normal murine splenic B lymphocytes demonstrates that they also possess high-affinity receptors for PGE2. Treatment of normal B cells with IL-4 increased PGE2 receptor levels fourfold from approximately 50 to 200 sites/cell while the affinity of the receptor slightly decreased. These results are the first to describe the number and affinity of PGE2 receptors on cells of the B lineage. These findings also suggest that B lymphocyte-activating molecules such as LPS and IL-4 may enhance sensitivity to PGE2 by upregulating the number of PGE2 receptors on B cells. Moreover, these observations may be of importance in developing strategies to specifically control the spread of PGE2-sensitive B lymphomas.
前列腺素E2（PGE2）是一种多效性脂质分子，由巨噬细胞、滤泡树突状细胞和成纤维细胞合成，这些细胞均存在于B细胞微环境中。它是B淋巴细胞功能的有效调节剂，包括激活和免疫球蛋白类别转换。为了了解PGE2对B淋巴细胞功能的影响，必须明确B谱系细胞上假定的PGE2受体的特征。该受体尚未在B淋巴细胞上得到表征。小鼠B细胞淋巴瘤被用作评估B谱系PGE2受体的模型，因为它们在响应PGE2时会升高细胞内cAMP。Scatchard分析表明，CH31和CH12上的PGE2受体均以单一高亲和力状态存在，与CH31相比，CH12 B淋巴瘤每个细胞的受体数量多三倍。有趣的是，PGE2受体受到调控，因为20小时的LPS处理使CH12和CH31 B细胞淋巴瘤上的PGE2受体数量增加了两到三倍，而解离常数保持相似。最后，对正常小鼠脾脏B淋巴细胞的Scatchard分析表明，它们也具有PGE2的高亲和力受体。用IL-4处理正常B细胞可使PGE2受体水平从约50个位点/细胞增加四倍至200个位点/细胞，而受体的亲和力略有下降。这些结果首次描述了B谱系细胞上PGE2受体的数量和亲和力。这些发现还表明，诸如LPS和IL-4等B淋巴细胞激活分子可能通过上调B细胞上PGE2受体的数量来增强对PGE2的敏感性。此外，这些观察结果对于制定特异性控制PGE2敏感B淋巴瘤扩散的策略可能具有重要意义。
