Paul Elahna, Lutz Johannes, Erikson Jan, Carroll Michael C
Department of Pediatrics, Harvard Medical School, Division of Nephrology, Children's Hospital and Center for Blood Research, Boston, MA 02115, USA.
Int Immunol. 2004 Feb;16(2):377-84. doi: 10.1093/intimm/dxh035.
Regulation throughout B cell maturation and activation prevents autoreactive B cells from entering germinal center (GC) reactions. This study shows that a subset of autoreactive B cells in V(H)3H9 micro IgH transgenic mice escapes these serial checkpoints and proceeds into splenic GC. GC B cells isolated from these mice all express the transgenic V(H)3H9 micro heavy chain, some co-express light chains that yield an anti-dsDNA specificity and some have somatic mutations, consistent with their GC origin. Nonetheless, B cell tolerance is ultimately preserved as serum titers of anti-dsDNA antibodies are not elevated. These observations suggest that those autoreactive GC B cells that escaped earlier checkpoints and possibly also those cells that acquire autoreactivity de novo by mutating their antigen receptor are arrested within the splenic GC before differentiating further into antibody-secreting plasma cells.
在整个B细胞成熟和激活过程中的调控可防止自身反应性B细胞进入生发中心（GC）反应。本研究表明，V(H)3H9微小IgH转基因小鼠中的一部分自身反应性B细胞逃避了这些连续的检查点，并进入脾脏GC。从这些小鼠中分离出的GC B细胞均表达转基因V(H)3H9微小重链，一些细胞共表达产生抗双链DNA特异性的轻链，还有一些细胞具有体细胞突变，这与其GC起源一致。尽管如此，由于抗双链DNA抗体的血清滴度没有升高，B细胞耐受性最终得以维持。这些观察结果表明，那些逃避了早期检查点的自身反应性GC B细胞，以及那些可能通过其抗原受体突变而重新获得自身反应性的细胞，在进一步分化为分泌抗体的浆细胞之前，被阻滞在脾脏GC内。
