Kimata H, Yoshida A, Ishioka C, Fujimoto M, Lindley I, Furusho K
Department of Pediatrics, Yunichika Central Hospital, Kyoto, Japan.
J Exp Med. 1996 May 1;183(5):2397-402. doi: 10.1084/jem.183.5.2397.
We studied the effects of various chemokines including neutrophil-activating peptide 2 (NAP-2), beta-thromboglobulin (beta-TG), platelet factor 4 (PF-4), melanoma growth stimulating activity (GRO), gamma interferon-induced protein (IP-10), regulated on activation, normal T expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and monocyte chemotactic protein 1 (MCP-1) on Immunoglobulin (IgE) and IgG4 production by human B cells. None of these chemokines with or without interleukin (IL-4), anti-CD40 or -CD58 monoclonal antibody (mAb), induced IgE and IgG4 production by B cells from nonatopic donors. However, RANTES and MIP-1 alpha selectively enhanced IgE and IgG4 production induced by IL-4 plus anti-CD40 or -CD58 mAb without affecting production of IgM, IgG1, IgG2, IgG3, IgA1, or IgA2, whereas other chemokines failed to do so. Enhancement of IgE and IgG4 production by RANTES and MIP-1 alpha was specifically blocked by anti-RANTES mAb and anti-MIP-1 alpha antibody (Ab), respectively, whereas anti-IL-5 mAb, anti-IL-6 mAb, anti-IL-10 Ab, anti-IL-13 Ab, and anti-tumor necrosis factor-alpha mAb failed to do so. Purified surface IgE positive (slgE4) and slgG4+ B cells generated either in vitro or in vivo spontaneously produced IgE and IgG4, respectively, whereas sIgE- and sIgG4- B cells failed to do so. RANTES and MIP-1 alpha enhanced spontaneous IgE and IgG4 production in slgE+ and slgG4- B cells, respectively, whereas neither RANTES nor MIP-1 alpha did so in sIgE- or sIgG4- B cells. Purified sIgE4+ and sIgG4+, but not sIgE- or sIgG4- B cells, generated in vitro and in vivo expressed receptors for RANTES and MIP-1 alpha, whereas they failed to express receptors for other chemokines. These findings indicate that RANTES and MIP-1 alpha enhance IgE and IgG4 production by directly stimulating sIgE+ and sIgG4+ B cells.
我们研究了多种趋化因子,包括中性粒细胞激活肽2(NAP - 2)、β - 血小板球蛋白(β - TG)、血小板因子4(PF - 4)、黑素瘤生长刺激活性因子(GRO)、γ干扰素诱导蛋白(IP - 10)、激活调节正常T细胞表达和分泌因子(RANTES)、巨噬细胞炎性蛋白1α(MIP - 1α)、MIP - 1β以及单核细胞趋化蛋白1(MCP - 1)对人B细胞免疫球蛋白(IgE)和IgG4产生的影响。这些趋化因子单独或与白细胞介素(IL - 4)、抗CD40或抗CD58单克隆抗体(mAb)联合使用时,均不能诱导非特应性供体B细胞产生IgE和IgG4。然而,RANTES和MIP - 1α能选择性增强由IL - 4加抗CD40或抗CD58 mAb诱导的IgE和IgG4产生,且不影响IgM、IgG1、IgG2、IgG3、IgA1或IgA2的产生,而其他趋化因子则无此作用。RANTES和MIP - 1α对IgE和IgG4产生的增强作用分别被抗RANTES mAb和抗MIP - 1α抗体(Ab)特异性阻断,而抗IL - 5 mAb、抗IL - 6 mAb、抗IL - 10 Ab、抗IL - 13 Ab和抗肿瘤坏死因子 - α mAb则无此作用。体外或体内产生的纯化表面IgE阳性(slgE4)和slgG4 + B细胞分别自发产生IgE和IgG4,而sIgE - 和sIgG4 - B细胞则不能。RANTES和MIP - 1α分别增强slgE + 和slgG4 - B细胞中的自发IgE和IgG4产生,而RANTES和MIP - 1α对sIgE - 或sIgG4 - B细胞均无此作用。体外和体内产生的纯化sIgE4 + 和sIgG4 + B细胞表达RANTES和MIP - 1α的受体,但不表达其他趋化因子的受体。这些发现表明,RANTES和MIP - 1α通过直接刺激sIgE + 和sIgG4 + B细胞来增强IgE和IgG4的产生。