STRUCTURE OF THE V(H) AND V(L) SEGMENTS OF POLYREACTIVE AND MONOREACTIVE HUMAN NATURAL ANTIBODIES TO HIV-1 AND ESCHERICHIA-COLI BETA-GALACTOSIDASE
STRUCTURE OF THE V(H) AND V(L) SEGMENTS OF POLYREACTIVE AND MONOREACTIVE HUMAN NATURAL ANTIBODIES TO HIV-1 AND ESCHERICHIA-COLI BETA-GALACTOSIDASE
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DOI：
10.1093/intimm/5.12.1523
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发表时间：
1993-12-01
影响因子：
4.4
通讯作者：
CASALI, P
中科院分区：
文献类型：
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作者：
HARINDRANATH, N;IKEMATSU, H;CASALI, P
致力于产生与病原细菌和病毒抗原结合的抗体(天然抗体)的B淋巴细胞是正常人类B细胞库的常见成分。大部分天然抗体能够结合多种抗原(多反应抗体)。用3例HIV-1血清阴性健康受试者的B细胞，以纯化的HIV-1和大肠杆菌β-半乳糖苷酶为选择抗原，制备了3株天然的抗HIV-1的IgM单抗和1株天然的抗-β-半乳糖苷酶的IgM单抗。三种HIV-1选择的抗体(mAb102、mAb103和mAb104)具有多反应性。它们以不同的亲和力(K(D)=10(-6)~10(-8)M)与HIV-1包膜蛋白gp160、p24核心蛋白和p66逆转录酶结合，但不与120糖化的env蛋白结合。它们还与β-半乳糖苷酶(K(D)约10(-7)M)、破伤风类毒素和各种自身抗原结合。相反，选择与β-半乳糖苷酶(mAb207.F1)结合的天然单抗是单反应的，因为它与该抗原结合有高亲和力(K(D)和lt；10(-8)M)，但不与包括HIV-1在内的其他被测抗原结合。对V(H)和V(L)片段的结构分析表明，该天然单抗利用了V(H)IV基因家族的三个片段和V(H)III家族的一个片段，以及V(L)V(Lambda)I、V(Lambda)II、V(Lambda)III或V(Chi)IV亚群的V(L)片段。此外，天然mAbV(H)和V(L)片段处于未突变或几乎未突变(胚系)的构型，包括对β-半乳糖苷酶具有单反应活性的mAb207.F1的那些片段，并且与特定的自身抗体或针对病毒和/或细菌病原体的特异性抗体所利用的片段相同或密切相关。因此，目前的数据表明，针对外来抗原的多反应和单反应的天然抗体都可以从正常人类B细胞库中分离出来。他们还提示，不仅多反应而且单反应的天然抗体的V(H)和V(L)片段可以在未突变或最小突变的基因中编码，并可能为自身或外来抗原诱导的特异性高亲和力抗体提供模板。
B lymphocytes committed to the production of antibodies binding to antigens on pathogenic bacteria and viruses (natural antibodies) are common components of the normal human B cell repertoire. A major proportion of natural antibodies is capable of binding multiple antigens (polyreactive antibodies). Using B cells from three HIV-1 seronegative healthy subjects, and purified HIV-1 and beta-galactosidase from Escherichia coli as selecting antigen, we generated three natural IgM mAb to HIV-1 and a natural IgM mAb to beta-galactosidase. The three HIV-1-selected antibodies (mAb102, mAb103, and mAb104) were polyreactive. They bound with different affinities (K(d) = 10(-6) to 10(-8) M) to the HIV-1 envelope gp160, the p24 core protein, and the p66 reverse transcriptase, but not to the 120 glycosilated env protein. They also bound to beta-galactosidase (K(d) approximately 10(-7) M), tetanus toxoid, and various self antigens. In contrast, the natural mAb selected for binding to beta-galactosidase (mAb207.F1) was monoreactive, in that it bound with a high affinity (K(d) < 10(-8) M) to this antigen, but to none of the other antigens tested, including HIV-1. Structural analysis of the V(H) and V(L) segments revealed that the natural mAb utilized three segments of the V(H)IV gene family and one of the V(H)III family, in conjunction with V(L) segments of the V(lambda)I, V(lambda)II, V(lambda)III, or V(chi)IV subgroups. In addition, the natural mAb V(H) and V(L) segments were in unmutated or virtually unmutated (germline) configuration, including those of the monoreactive mAb207.F1 to beta-galactosidase, and were identical or closely related to those utilized by specific autoantibodies or specific antibodies to viral and/or bacterial pathogens. Thus, the present data show that both polyreactive and monoreactive natural antibodies to foreign antigen can be isolated from the normal human B cell repertoire. They also suggest that the V(H) and V(L) segments of not only polyreactive but also monoreactive natural antibodies can be encoded in unmutated or minimally mutated genes, and possibly provide the templates for the specific high affinity antibodies elicited by self or foreign antigens.