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Immunofluorescence analysis of splenic leukocytes showed no significant differences in the percentage of T cell subsets, B cells, or macrophages between wild-type and CB1\u2212\/\u2212\/CB2\u2212\/\u2212 mice. Lymphoproliferative control responses to PHA, phorbol ester plus ionomycin, or LPS and sensitivity to suppression by \u03949-THC showed no profound differences between the two genotypes, although some differences were observed in control baseline responses. Likewise, similar control responses and sensitivity to \u03949-THC were observed in mixed lymphocyte responses (MLR) and in IL-2 and IFN-\u03b3 production in both genotypes. Conversely, humoral immune responses showed a markedly different profile of activity. \u03949-THC suppressed the in vivo T cell-dependent, anti-sheep RBC (anti-sRBC) IgM antibody-forming cell (AFC) response in wild-type but not in CB1\u2212\/\u2212\/CB2\u2212\/\u2212 mice, and the in vitro anti-sRBC IgM response in CB1\u2212\/\u2212\/CB2\u2212\/\u2212 splenocytes was too low to rigorously assess CB1\/CB2 involvement in modulation by \u03949-THC. Conversely, comparable in vitro IgM AFC control responses to LPS and CD40 ligand (CD40L) activation were observed in the two genotypes. Interestingly, LPS-induced IgM responses were refractory to suppression by \u03949-THC, regardless of genotype, and CD40L-induced IgM responses were only suppressed by \u03949-THC in wild-type but not in CB1\u2212\/\u2212\/CB2\u2212\/\u2212 B cells. Collectively, we demonstrate differential involvement of CB1 and\/or CB2 in immune modulation by \u03949-THC and in some control responses. Moreover, CB1\/CB2 involvement was observed in humoral responses requiring CD40-initiated signaling for suppression by \u03949-THC.<\/jats:p>","DOI":"10.1189\/jlb.0508282","type":"journal-article","created":{"date-parts":[[2008,9,13]],"date-time":"2008-09-13T01:06:54Z","timestamp":1221268014000},"page":"1574-1584","source":"Crossref","is-referenced-by-count":38,"title":["Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by \u03949-tetrahydrocannabinol"],"prefix":"10.1093","volume":"84","author":[{"given":"Alison E B","family":"Springs","sequence":"first","affiliation":[{"name":"Center for Integrative Toxicology, Cell and Molecular Biology Program , Michigan , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peer W F","family":"Karmaus","sequence":"additional","affiliation":[{"name":"Center for Integrative Toxicology, Cell and Molecular Biology Program , Michigan , USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University , East Lansing, Michigan , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Michigan State University , East Lansing, Michigan , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara L F","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Center for Integrative Toxicology, Cell and Molecular Biology Program , Michigan , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert E","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Center for Integrative Toxicology, Cell and Molecular Biology Program , Michigan , USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University , East Lansing, Michigan , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,9,12]]},"reference":[{"key":"2023032712375338600_","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1021\/ja01062a046","article-title":"Isolation, structure and partial synthesis of an active constituent of hashish","volume":"86","author":"Gaoni","year":"1964","journal-title":"J. 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