Gearhart P J, Cebra J J
J Exp Med. 1979 Jan 1;149(1):216-27. doi: 10.1084/jem.149.1.216.
B cells have the potential to respond to an antigen by producing antibodies with a variety of variable and constant regions. We have quantitatively analyzed B-cell potential at the single cell level to determine the effect of lymphoid tissue site and antigen load on the expression of variable and constant regions. Concerning variable region expression, although the total frequency of B-cell precursors for phosphorylcholine is similar between nonimmune spleen and gut-associated Peyer's patch tissues, the proportion of cells producing non-TEPC 15 idiotypes is greater from Peyer's patch than from spleen. Oral immunization with phosphorylcholine-containing Ascaris suum increased the frequency of non-TEPC 15 B cells. Thus variation in the proportion of cells bearing different variable regions may be related to the distinct antigenic environment of cells in Peyer's patches compared to that of cells in spleen. Regarding constant region expression, although B cells from both spleen and Peyer's patches generate clones producing IgM, IgGl, and IgA singly and in all combinations, cells from Peyer's patches generate more clones secreting only IgA than cells from spleen. B cells specific for phosphorylcholine and inulin, which are found on intestinal bacteria, produce more IgA-only clones than B cells specific for the dinitrophenyl determinant. This striking correlation between IgA expression and variable region specificity for antigen implies that environmental antigens have expanded certain B cells in Peyer's patches which then have the ability to generate progeny that express only IgA. Evidence supporting the secondary nature of precursors for IgA-only clones is obtained by their ability to produce this isotype after stimulation with histoincompatible T cells. The role of gut antigens may be to clonally expand IgA precursors and perhaps to stimulate the proliferation of less differentiated cells within the unique microenvironment of the Peyer's patches, allowing them to differentiate to IgA precursors.
B细胞有潜力通过产生具有多种可变区和恒定区的抗体来对抗抗原。我们在单细胞水平上对B细胞潜力进行了定量分析，以确定淋巴组织部位和抗原负荷对可变区和恒定区表达的影响。关于可变区表达，尽管磷酸胆碱的B细胞前体在非免疫脾脏和肠道相关派尔集合淋巴结组织中的总频率相似，但派尔集合淋巴结中产生非TEPC 15独特型的细胞比例高于脾脏。用含磷酸胆碱的猪蛔虫进行口服免疫增加了非TEPC 15 B细胞的频率。因此，与脾脏细胞相比，携带不同可变区的细胞比例的差异可能与派尔集合淋巴结中细胞独特的抗原环境有关。关于恒定区表达，尽管来自脾脏和派尔集合淋巴结的B细胞都能产生单独和所有组合形式分泌IgM、IgG1和IgA的克隆，但派尔集合淋巴结中的细胞比脾脏中的细胞产生更多仅分泌IgA的克隆。对存在于肠道细菌上的磷酸胆碱和菊粉具有特异性的B细胞，比针对二硝基苯基决定簇具有特异性的B细胞产生更多仅分泌IgA的克隆。IgA表达与抗原可变区特异性之间的这种显著相关性表明，环境抗原在派尔集合淋巴结中使某些B细胞扩增，这些B细胞随后有能力产生仅表达IgA的后代。通过它们在与组织不相容的T细胞刺激后产生这种同种型的能力，获得了支持仅分泌IgA克隆的前体具有继发性的证据。肠道抗原的作用可能是使IgA前体进行克隆性扩增，也许还能刺激派尔集合淋巴结独特微环境中分化程度较低的细胞增殖，使它们分化为IgA前体。
