Hu Lina, Rezanka Louis J, Mi Qing-Sheng, Lustig Ana, Taub Dennis D, Longo Dan L, Kenny James J
Laboratory of Immunology, Gerontology Research Center, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
J Immunol. 2002 Feb 1;168(3):1273-80. doi: 10.4049/jimmunol.168.3.1273.
T15i knockin (KI) mice express a H chain that is encoded by a rearranged T15 VDJ transgene which has been inserted into the J(H) region of chromosome 12. This T15H chain combines with a kappa22-33 L chain to produce a T15-Id+ Ab having specificity for phosphocholine (PC). Inasmuch as T15-Id+ Abs dominate the primary immune response to PC in normal mice, it was surprising to find that 80% of the PC-dextran-binding B cells in unimmunized homozygous T15i KI mice were T15-Id-. Analysis of L chains expressed in these T15-Id-, PC-specific B cells revealed that two L chains, kappa8-28 and kappa19-15, were expressed in this population. The V(kappa) region of these L chains was recombined to J(kappa)5, which is typical of L chains present in PC-specific Abs. When T15i KI mice were immunized with PC Ag, T15-Id+ B cells expanded 6-fold and differentiated into Ab-secreting cells. There was no indication that the T15-Id- B cells either proliferated or differentiated into Ab-secreting cells following immunization. Thus, T15-Id- B cells dominate the PC-binding population, but they fail to compete with T15-Id+ B cells during a functional immune response. Structural analysis of T15H:kappa8-28L and T15H:kappa19-15L Abs revealed L chain differences from the kappa22-33 L chain which could account for the lower affinity and/or avidity of these Abs for PC or PC carrier compared with the T15-Id+ T15H:kappa22-33L Ab.
T15i敲入(KI)小鼠表达一种重链,该重链由插入到12号染色体J(H)区域的重排T15 VDJ转基因编码。这种T15重链与kappa22 - 33轻链结合,产生对磷酸胆碱(PC)具有特异性的T15 - Id +抗体。由于T15 - Id +抗体在正常小鼠对PC的初次免疫反应中占主导地位,所以令人惊讶地发现,未免疫的纯合T15i KI小鼠中80%与PC - 葡聚糖结合的B细胞是T15 - Id - 。对这些T15 - Id - 、PC特异性B细胞中表达的轻链分析表明,该群体中表达了两种轻链,kappa8 - 28和kappa19 - 15。这些轻链的V(kappa)区域与J(kappa)5重排,这是PC特异性抗体中存在的轻链的典型特征。当用PC抗原免疫T15i KI小鼠时,T15 - Id + B细胞扩增6倍并分化为抗体分泌细胞。没有迹象表明免疫后T15 - Id - B细胞增殖或分化为抗体分泌细胞。因此,T15 - Id - B细胞在与PC结合的群体中占主导,但在功能性免疫反应中它们无法与T15 - Id + B细胞竞争。对T15H:kappa8 - 28L和T15H:kappa19 - 15L抗体的结构分析表明,其轻链与kappa22 - 33轻链存在差异,这可能解释了与T15 - Id + T15H:kappa22 - 33L抗体相比,这些抗体对PC或PC载体的亲和力和/或avidity较低的原因。