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CD Id is a nonpolymorphic, MHC class I-like molecule that presents phospholipid and glycosphingolipid Ags to a subset of CD 1 d-restricted T cells called invariant NKT (iNKT) cells. This CDld-iNKT cell axis regulates nearly all aspects of both the innate and adaptive immune responses. Expression of CD Id on B cells is suggestive of the ability of these cells to present Ag to, and form cognate interactions with, iNKT cells. In this article, we summarize key evidence regarding the role and regulation of CD Id in normal B cells and in humoral immunity. We then extend the discussion to B cell disorders, with emphasis on autoimmune disease, viral infection, and neoplastic transformation of B lineage cells, in which CD Id expression can be altered as a mechanism of immune evasion and can have both diagnostic and prognostic importance. Finally, we highlight current and future therapeutic strategies that aim to target the CDld-iNKT cell axis in B cells. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the major cause of morbidity and nonrelapse mortality after BM transplantation (BMT). The Paneth cell protein regenerating islet-derived 3α (REG3α) is a biomarker specific for GI GVHD. REG3α serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3γ (the mouse homolog of human REG3α), and the absence of REG3γ in BMT recipients intensified GVHD but did not change the composition of the microbiome. IL-22 administration restored REG3γ production and prevented apoptosis of both intestinal stem cells (ISCs) and Paneth cells, but this protection was completely abrogated in Reg3g-/- mice. In vitro, addition of REG3α reduced the apoptosis of colonic cell lines. Strategies that increase intestinal REG3α/γ to promote crypt regeneration may offer a novel, nonimmunosuppressive approach for GVHD and perhaps for other diseases involving the ISC niche, such as inflammatory bowel disease. [ABSTRACT FROM AUTHOR]