TY - JOUR
T1 - NKT-cell help to B lymphocytes can occur independently of cognate interaction
AU - Tonti, Elena
AU - Galli, Grazia
AU - Malzone, Carmine
AU - Abrignani, Sergio
AU - Casorati, Giulia
AU - Dellabona, Paolo
PY - 2009/1/8
Y1 - 2009/1/8
N2 - 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 αgalactosylceramide (αGalCer) presented by CD1d, and can help B-cell responses. We asked whether ivGalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B-cell interaction. After immunization with protein Ags and vGalCer, 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 αGalCer- 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 αGalCer-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 αGalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses.
AB - 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 αgalactosylceramide (αGalCer) presented by CD1d, and can help B-cell responses. We asked whether ivGalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B-cell interaction. After immunization with protein Ags and vGalCer, 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 αGalCer- 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 αGalCer-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 αGalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses.
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U2 - 10.1182/blood-2008-06-166249
DO - 10.1182/blood-2008-06-166249
M3 - Article
C2 - 18832653
AN - SCOPUS:58849166273
VL - 113
SP - 370
EP - 376
JO - Blood
JF - Blood
SN - 0006-4971
IS - 2
ER -