NKT-cell help to B lymphocytes can occur independently of cognate interaction

作者：Tonti Elena; Galli Grazia; Malzone Carmine; Abrignani Sergio; Casorati Giulia^*; Dellabona Paolo

来源：Blood, 2009, 113(2): 370-376.

DOI：10.1182/blood-2008-06-166249

CD4(+) T (Th)-cell help to B lymphocytes requires cognate interaction and CD40 engagement. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that recognize alpha galactosylceramide (alpha GalCer) presented by CD1d, and can help B-cell responses. We asked whether alpha GalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B-cell interaction. After immunization with protein Ags and alpha GalCer, antibody titers were assessed in wild-type or splenectomized mice, and in bone marrow radiation chimeras lacking CD1d or CD40 expression on B lymphocytes, or expressing CD1d or MHC II disjointly on antigen-presenting cells (APCs). We find that alpha GalCer-dependent enhancement of B-cell response (1) can occur when B cells do not express CD1d but express CD40; (2) requires that iNKT and Th cells interact with the same APCs that coexpress both CD1d and MHC-II; and (3) takes place without spleen. These findings demonstrate alpha GalCer-induced help for antibody responses can occur without cognate iNKT/B-cell interaction, and suggest this help entails activation of APCs by iNKT cells, which in turn activate Th cells and their helper functions for B cells. Thus, the alpha GalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses. (Blood. 2009;113:370-376)

• 出版日期2009-1-8