Wither J E, Roy V, Brennan L A
The Arthritis Centre of Excellence, The Toronto Hospital Research Institute, The Toronto Hospital-Western Division, Canada.
Clin Immunol. 2000 Jan;94(1):51-63. doi: 10.1006/clim.1999.4806.
Polyclonal B cell activation is a hallmark of autoimmune disease in NZB and (NZB x NZW)F(1) (NZB/W) mice. However, the mechanism by which this activated cell subset facilitates disease development is unknown. We recently showed that resting B cells from these mice demonstrate enhanced expression of costimulatory molecules in response to CD40 crosslinking (Jongstra-Bilen et al., J. Immunol. 159,5810-5820, 1997). This led us to question whether activated B cells expressed costimulatory molecules in vivo. Using flow cytometry we found that NZB and NZB/W mice have an increased proportion of splenic B cells expressing B7.1 and elevated levels of B7.2 and ICAM-1. These B cells isolate within the low-density activated population and possess the phenotypic characteristics of marginal zone B cells. The levels of B7.1 on the activated B cell population are similar to those induced by CD40 stimulation raising the possibility that activated B cells in NZB and NZB/W mice provide costimulatory signals to self-reactive T cells leading to loss of tolerance.
多克隆B细胞活化是NZB和（NZB×NZW）F1（NZB/W）小鼠自身免疫性疾病的一个标志。然而，这种活化的细胞亚群促进疾病发展的机制尚不清楚。我们最近发现，来自这些小鼠的静息B细胞在CD40交联后表现出共刺激分子表达增强（Jongstra - Bilen等人，《免疫学杂志》159,5810 - 5820，1997）。这使我们质疑活化的B细胞在体内是否表达共刺激分子。通过流式细胞术，我们发现NZB和NZB/W小鼠脾脏中表达B7.1的B细胞比例增加，且B7.2和ICAM - 1水平升高。这些B细胞在低密度活化群体中分离出来，并具有边缘区B细胞的表型特征。活化B细胞群体上B7.1的水平与CD40刺激诱导的水平相似，这增加了NZB和NZB/W小鼠中活化的B细胞向自身反应性T细胞提供共刺激信号从而导致免疫耐受丧失的可能性。
