Basu Sreemanti, Ray Avijit, Dittel Bonnie N
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America ; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
PLoS One. 2013 Jun 27;8(6):e67587. doi: 10.1371/journal.pone.0067587. Print 2013.
The cannabinoid receptor 2 (CB2) has been reported to modulate B cell functions including migration, proliferation and isotype class switching. Since these processes are required for the generation of the germinal center (GC) and antigen-specific plasma and memory cells following immunization with a T-dependent antigen, CB2 has the capacity to alter the quality and magnitude of T-dependent immune responses. To address this question, we immunized WT and CB2(-/-) mice with the T-dependent antigen 4-hydroxy-3-nitrophenylacetyl (NP)-chicken-gamma-globulin (CGG) and measured GC B cell formation and the generation of antigen-specific B cells and serum immunoglobulin (Ig). While there was a significant reduction in the number of splenic GC B cells in CB2(-/-) mice early in the response there was no detectable difference in the number of NP-specific IgM and IgG1 plasma cells. There was also no difference in NP-specific IgM and class switched IgG1 in the serum. In addition, we found no defect in the homing of plasma cells to the bone marrow (BM) and affinity maturation, although memory B cell cells in the spleen were reduced in CB2(-/-) mice. CB2-deficient mice also generated similar levels of antigen-specific IgM and IgG in the serum as WT following immunization with sheep red blood cells (sRBC). This study demonstrates that although CB2 plays a role in promoting GC and memory B cell formation/maintenance in the spleen, it is dispensable on all immune cell types required for the generation of antigen-specific IgM and IgG in T-dependent immune responses.
据报道，大麻素受体2（CB2）可调节B细胞功能，包括迁移、增殖和同种型类别转换。由于在用T细胞依赖性抗原免疫后生发中心（GC）以及抗原特异性浆细胞和记忆细胞的产生需要这些过程，因此CB2有能力改变T细胞依赖性免疫反应的质量和强度。为了解决这个问题，我们用T细胞依赖性抗原4-羟基-3-硝基苯乙酰（NP）-鸡γ球蛋白（CGG）免疫野生型（WT）和CB2基因敲除（-/-）小鼠，并测量GC B细胞的形成以及抗原特异性B细胞和血清免疫球蛋白（Ig）的产生。虽然在反应早期CB2基因敲除小鼠脾脏中GC B细胞数量显著减少，但NP特异性IgM和IgG1浆细胞数量没有可检测到的差异。血清中NP特异性IgM和类别转换的IgG1也没有差异。此外，我们发现浆细胞归巢至骨髓（BM）和亲和力成熟方面没有缺陷，尽管CB2基因敲除小鼠脾脏中的记忆B细胞减少。在用绵羊红细胞（sRBC）免疫后，CB2缺陷小鼠血清中产生的抗原特异性IgM和IgG水平也与野生型小鼠相似。这项研究表明，虽然CB2在促进脾脏中GC和记忆B细胞的形成/维持中发挥作用，但在T细胞依赖性免疫反应中产生抗原特异性IgM和IgG所需的所有免疫细胞类型中，它并非必需。
