Rabbit Anti-Mouse LY6A monoclonal antibody, clone KN64-22

Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines(1,2). Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors(3) and lymphoid tissue inducer cells(4). These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells(5-7). Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection(8,9). After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.

Strain-specific differences in susceptibility to mouse adenovirus type 1 (MAV-1) are linked to the quantitative trait locus Msq1 on mouse chromosome 15. This region contains 14 Ly6 or Ly6-related genes, many of which are known to be expressed on the surface of immune cells, suggesting a possible role in host defense. We analyzed these genes for polymorphisms between MAV-1-susceptible and MAV-1-resistant inbred mouse strains. Sequencing of cDNAs identified 12 coding-region polymorphisms in 2010109I03Rik, Ly6e, Ly6a, Ly6c1, and Ly6c2, six of which were nonsynonymous and five of which were previously unlisted in dbSNP Build 132. We also clarified sequence discrepancies in GenBank for the coding regions of I830127L07Rik and Ly6g. Additionally, Southern blotting revealed size polymorphisms within the DNA regions of Ly6e, Ly6a, and Ly6g. Collectively, these genetic variations have implications for the structure, function, and/or expression of Ly6 and Ly6-related genes that may contribute to the observed strain-specific differences in susceptibility to MAV-1.