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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]

Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies. Herein, we report a family in which a wide range of systemic inflammatory and neoplastic manifestations have occurred across three generations. We found that disease was linked to two missense perforin gene mutations (encoding A91V, R410W) that cause protein misfolding and partial loss of activity. These cases link the partial loss of perforin function with some solid tumors that are known to be controlled by the immune system, as well as haematological cancers. Our findings also demonstrate that perforin gene mutations can contribute to hereditary cancer predisposition. [ABSTRACT FROM AUTHOR]