Regulation of Immune Responses by the Activating and Inhibitory Myeloid-Associate Immunoglobuline-Like Receptors (MAIR) (CD300)

Activating and inhibitory cell surface receptors play important roles in regulation of immune responses. Recent progress has demonstrated that many inhibitory receptors pair with activating, as well as inhibitory, isoforms, both of whose genes are located in small clusters on a chromosome. We and others identified paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptors (MAIR) (CD300). MAIR is a multigene family consisting of nine genes on a small segment of mouse chromosome 11. MAIR family receptors are preferentially expressed on myeloid cells, including macrophages, dendritic cells, granulocytes, and bone-marrow-derived cultured mast cells, and a subset of B cells and regulate activation of these cells. Thus, MAIR plays an important role in innate immunity mediated by myeloid cells

Isolation and characterization of naïve follicular dendritic cells

Follicular dendritic cells (FDC) are specialized antigen-presenting cells to cognate B cells in the follicle of the lymphoid tissues. FDC also support survival and proliferation of the B cells, leading to the germinal center formation. FDC therefore play a central role in humoral immune responses. However, molecular and functional characteristics of FDC are largely unknown, because it is difficult to isolate and analyze FDC due to a very small number of FDC in the lymphoid tissues and the fragility by mechanical and chemical stresses in vitro. In this report, we established a novel method for FDC isolation from the spleen of naïve mice by flow cytometry and analyzed the phenotypical and functional characteristics. The isolated FDC, which accounted for ∼0.2% of the spleen cells of naïve mice, were CD45−, FDC-M2+, and ICAM-1+, and supported the survival and LPS-induced proliferation of B cells. We also showed that a neutralizing antibody against B cell activating factor TNF family (BAFF) suppressed FDC-dependent B cell proliferation in the presence of LPS, but not survival, demonstrating the evidence that FDC-derived BAFF is involved in B cell proliferation

The immunoreceptor adapter protein DAP12 suppresses B lymphocyte–driven adaptive immune responses

Human and mouse B cells lacking functional DAP12 are hyperresponsive, and DAP12 works with MAIR-II (CD300d) to negatively regulate B cell activity