Nitschke L, Carsetti R, Ocker B, Köhler G, Lamers M C
Max-Planck-Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany.
Curr Biol. 1997 Feb 1;7(2):133-43. doi: 10.1016/s0960-9822(06)00057-1.
. Antibody responses are triggered by binding of antigen to the B-cell antigen receptor (BCR). The strength of the resulting signal determines the outcome of the response, which may vary from the induction of tolerance to the antigen, to the production of specific high-affinity antibodies. Additional cell-surface proteins assist the BCR in its function, and can facilitate or inhibit an antibody response. CD22 is a BCR-associated transmembrane protein, the cytoplasmic tail of which contains three immunoreceptor tyrosine-based inhibitory motifs. These motifs are phosphorylated upon BCR-crosslinking, and can bind the tyrosine phosphatase SHP-1, a putative negative regulator of signalling from the BCR. In order to assess the role of CD22 in vivo, we have generated CD22(-/-) mice by targeted gene inactivation.
. In CD22(-/-) mice, B-cell development is normal. There are normal numbers of peripheral B cells, but these have a more mature phenotype. In addition, recirculating B cells are absent from the bone marrow. However, the distribution of the two B-cell subtypes, B-1 and B-2, is normal. After BCR-crosslinking in vitro, splenic CD22(-/-) B cells show an increased Ca2+ influx and a lower survival due to an increased induction of apoptosis. In contrast, there is an increased proliferative response to the B-cell mitogen lipopolysaccharide (LPS). A shorter average lifespan in the B-cell compartment is also found in vivo. Furthermore, T-cell independent immune responses are impaired, whereas T-cell dependent responses are normal.
. The absence of CD22 expression lowers the signalling threshold for BCR-crosslinking and can thus influence the fate of the B cell. We propose that the low threshold leads to hyperresponsiveness of the B cells and a chronic basal activation. In this model, engagement of the receptor without T-cell help leads to an increased induction of apoptosis, thus explaining the shorter lifespan of CD22(-/-) B cells and the low response to T-cell independent antigens. The alteration in B-cell phenotype and the higher levels of LPS-reactivity are attributable to the chronic basal stimulation.
抗体反应由抗原与B细胞抗原受体（BCR）结合触发。所产生信号的强度决定反应结果，反应结果可能从诱导对抗原的耐受性到产生特异性高亲和力抗体不等。其他细胞表面蛋白协助BCR发挥功能，并可促进或抑制抗体反应。CD22是一种与BCR相关的跨膜蛋白，其胞质尾部包含三个基于免疫受体酪氨酸的抑制基序。这些基序在BCR交联时被磷酸化，并可结合酪氨酸磷酸酶SHP-1，SHP-1是BCR信号传导的一种假定负调节因子。为了评估CD22在体内的作用，我们通过靶向基因失活产生了CD22(-/-)小鼠。
在CD22(-/-)小鼠中，B细胞发育正常。外周B细胞数量正常，但具有更成熟的表型。此外，骨髓中不存在再循环B细胞。然而，两种B细胞亚型B-1和B-2的分布正常。体外BCR交联后，脾CD22(-/-) B细胞显示Ca2+内流增加，且由于凋亡诱导增加而存活率降低。相反
