Serreze D V, Fleming S A, Chapman H D, Richard S D, Leiter E H, Tisch R M
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
J Immunol. 1998 Oct 15;161(8):3912-8.
Nonobese diabetic (NOD) mice genetically deficient in B lymphocytes (NODJg mu(null)) are resistant to T cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM). Ig infusions from diabetic NOD donors did not abrogate IDDM resistance in NODJg mu(null) mice. However, T cell responses to the candidate pancreatic beta cell autoantigen glutamic acid decarboxylase (GAD), but not the control Ag keyhole limpet hemocyanin, were eliminated in NODJg mu(null) mice. To initially test whether they contribute to IDDM as APC, NOD B lymphocytes were transferred into NODJg mu(null) recipients. B lymphocytes transferred into unmanipulated NODJg mu(null) recipients were rejected by MHC class I-restricted T cells. Stable T and B lymphocyte repopulation was achieved in irradiated NODJg mu(null) mice reconstituted with syngeneic bone marrow admixed with NOD B lymphocytes. IDDM susceptibility was restored in NODJg mu(null) mice reconstituted with syngeneic marrow plus B lymphocytes, but not with syngeneic marrow only. T cell responses to GAD were restored only in NODJg mu(null) mice reconstituted with syngeneic marrow plus B lymphocytes. Hence, B lymphocytes appear to contribute to IDDM in NOD mice as APC with a preferential ability to present certain beta cell Ags such as GAD to autoreactive T cells.
基因缺陷导致B淋巴细胞缺失的非肥胖型糖尿病（NOD）小鼠（NODJg mu(null)）对T细胞介导的自身免疫性胰岛素依赖型糖尿病（IDDM）具有抗性。来自糖尿病NOD供体的Ig输注并不能消除NODJg mu(null)小鼠对IDDM的抗性。然而，NODJg mu(null)小鼠中针对候选胰腺β细胞自身抗原谷氨酸脱羧酶（GAD）的T细胞反应被消除，但对对照抗原钥孔戚血蓝蛋白的反应未被消除。为了初步测试它们作为抗原呈递细胞（APC）是否对IDDM有影响，将NOD B淋巴细胞转移到NODJg mu(null)受体中。转移到未处理的NODJg mu(null)受体中的B淋巴细胞被MHC I类限制性T细胞排斥。在用同基因骨髓与NOD B淋巴细胞混合重建的受辐射NODJg mu(null)小鼠中实现了稳定的T和B淋巴细胞重建。用同基因骨髓加B淋巴细胞重建的NODJg mu(null)小鼠恢复了对IDDM的易感性，但仅用同基因骨髓重建的小鼠则没有。仅在用同基因骨髓加B淋巴细胞重建的NODJg mu(null)小鼠中恢复了对GAD的T细胞反应。因此，B淋巴细胞似乎作为APC在NOD小鼠的IDDM中起作用，具有将某些β细胞抗原（如GAD）优先呈递给自身反应性T细胞的能力。
