Roles of membrane-bound lectins in the regulation of immune cells.

CD22是siglec家族的成员，特异识别a2,6唾液酸，而CD72含有c型凝集素结构域。这些膜结合的凝集素分子在细胞质区域含有免疫受体酪氨酸基抑制基序（ITIMs）。磷酸化后，这些ITIMs招募并激活含有酪氨酸磷酸酶1 （SHP1）的SH2结构域，从而下调BCR信号传导。我们证明cd22介导的信号调节依赖于BCR的免疫球蛋白同型。事实上，CD22负调控IgM-BCR、IgD-BCR和IgA-BCR的信号传导，但不调控IgG-BCR或IgE-BCR的信号传导。在缺乏cd22介导的信号抑制的情况下，IgG-BCR和IgE-BCR传递增强的信号，这可能参与记忆反应中的快速抗体产生。细胞膜形式的IgG和IgE的细胞质区域参与cd22介导的信号抑制的消除。相比之下，CD72调节BCR信号，而不考虑Ig同型。SHP-1包含两个SH2结构域，CD22中3个ITIMs中至少有2个被认为是募集SHP-1所必需的。我们证明了一个ITIM足以招募SHP-1参与CD22和CD22介导的信号调节。此外，位于ITIM中位置783的酪氨酸似乎调节CD22细胞质区域中其他酪氨酸的磷酸化。这些发现对于阐明膜结合凝集素的功能和开发控制B细胞功能的新策略至关重要。

CD22 is a member of the siglec family and specifically recognizes a2,6 sialic acid, whereas CD72 contains a C-type lectin domain. These membrane-bound lectin molecules contain the immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region. Upon phosphorylation, these ITIMs recruit and activate the SH2 domain containing tyrosine phosphatase 1 (SHP1), thereby down-regulate BCR signaling. We demonstrated that CD22-mediated signal regulation depends on the immunoglobulin isotypes of BCR. Indeed, CD22 negatively regulates signaling through IgM-BCR, IgD-BCR and IgA-BCR, but not signaling through IgG-BCR or IgE-BCR. In the absence of CD22-mediated signaling inhibition, IgG-BCR and IgE-BCR transmit augmented signaling, which may be involved in rapid antibody production in memory responses. The cytoplasmic regions of membrane form of IgG and IgE are involved in abrogation of CD22-mediated signal inhibition. In contrast, CD72 regulates BCR signaling regardless of Ig isotypes. SHP-1 contains two SH2 domains, and at least two out of tree ITIMs in CD22 are suggested to be essential for recruitment of SHP-1. We demonstrated that one ITIM is sufficient for recruitment of SHP-1 to CD22 and CD22-mediated signal regulation. Moreover, tyrosine at the position 783 locating in an ITIM appears to regulate phosporylation of other tyrosines in the cytoplamic region of CD22. These findings are crucial for elucidation of the function of membrane-bound lectins, and development of new strategies for controlling B cell function.