Riley R L, Klinman N R
J Immunol. 1985 Nov;135(5):3050-5.
To evaluate the contribution of environmental regulatory mechanisms in fashioning the primary B cell repertoire, we have compared the repertoire of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific primary splenic B cells with that of precursor cells present as surface immunoglobulin-negative (sIg-) cells in adult bone marrow of C.B20 (Ighb) mice. Previous analyses using a variety of antigens have led to the conclusion that the antibody repertoire expressed in the spleen is similar to that expressed in newly generated B cell precursors with respect to both repertoire diversity and the representation of various predominant clonotypes. However, in the response to NP of C.B20 precursor cells, two marked disparities have been identified between the repertoire of sIg- bone marrow cells vs splenic precursor cells. The first concerns precursor cells that give rise to lambda-bearing NP-specific antibodies with heteroclitic fine specificity. Such antibodies normally dominate the primary response of Ighb mice; however, the representation of precursor cells giving rise to lambda-bearing antibodies is disproportionately low in the sIg- bone marrow cell population of C.B20 mice. Thus, during the maturation of these cells, post-sIg receptor expression, there is an apparent increase in the proportionate representation of lambda-bearing NP-specific cells. The second disparity concerns precursor cells whose antibody products bear kappa-light chains and exhibit high affinity and homoclitic binding for the NP haptenic determinant. Such precursor cells are poorly represented in the spleen, but represent a sizeable proportion of the sIg- NP-specific precursor cell population. Thus, there seems to be a selective elimination of high affinity, kappa-homoclitic anti-NP antibody-bearing cells as they acquire their sIg receptors. The elimination of this cell population could partially account for the dominance of lambda-heteroclitic antibodies in the serum responses to NP of C.B20 mice.
为了评估环境调节机制在塑造初始B细胞库中的作用，我们比较了(4-羟基-3-硝基苯基)乙酰(NP)特异性脾脏初始B细胞库与C.B20(Ighb)小鼠成年骨髓中作为表面免疫球蛋白阴性(sIg-)细胞存在的前体细胞库。先前使用多种抗原的分析得出结论，就库多样性和各种主要克隆型的代表性而言，脾脏中表达的抗体库与新生成的B细胞前体中表达的抗体库相似。然而，在C.B20前体细胞对NP的反应中，已确定sIg-骨髓细胞库与脾脏前体细胞库之间存在两个明显差异。第一个差异涉及产生具有异向性精细特异性的含λ链NP特异性抗体的前体细胞。此类抗体通常在Ighb小鼠的初始反应中占主导；然而，在C.B20小鼠的sIg-骨髓细胞群体中，产生含λ链抗体 的前体细胞的代表性极低。因此，在这些细胞成熟过程中，即sIg受体表达后，含λ链NP特异性细胞的比例代表性明显增加。第二个差异涉及抗体产物带有κ轻链并对NP半抗原决定簇表现出高亲和力和同向性结合的前体细胞。此类前体细胞在脾脏中的代表性较差，但在sIg-NP特异性前体细胞群体中占相当大的比例。因此，当高亲和力、κ同向性抗NP抗体的细胞获得其sIg受体时，似乎会被选择性清除。该细胞群体的清除可能部分解释了C.B20小鼠血清对NP反应中λ异向性抗体的主导地位。
