Cannabinoid Receptor 2 (CB2) Plays a Role in the Generation of Germinal Center and Memory B Cells, but Not in the Production of Antigen-Specific IgG and IgM, in Response to T-dependent Antigens.

Cannabinoid Receptor 2 (CB2) Plays a Role in the Generation of Germinal Center and Memory B Cells, but Not in the Production of Antigen-Specific IgG and IgM, in Response to T-dependent Antigens.
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DOI:
10.1371/journal.pone.0067587
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Dittel BN
Dittel BN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Basu S;Ray A;Dittel BN

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据报道,大麻素受体2(CB2)调节B细胞的功能,包括迁移、增殖和同型类转换。由于这些过程是在T依赖抗原免疫后产生生发中心(GC)和抗原特异的血浆和记忆细胞所必需的,因此CB2具有改变T依赖免疫反应的质量和大小的能力。为了解决这个问题,我们用T依赖抗原4-羟基-3-硝基苯乙酰(NP)-鸡丙种球蛋白(CGG)免疫WT和CB2−/−小鼠,并检测了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。Cb2−/−小鼠的脾GcB细胞数量在反应早期显著减少,但NP特异性免疫球蛋白M和免疫球蛋白G1浆细胞的数量没有明显差异。血清中NP特异性IgM和类转换型IgG1值也无差异。此外,尽管Cb2−/−小鼠脾中的记忆B细胞减少,但我们发现在浆细胞归巢到骨髓(BM)和亲和力成熟方面没有缺陷。CB2基因缺陷小鼠在绵羊红细胞(SRBC)免疫后,在血清中也产生了与WT相似的抗原特异性IgM和IgG水平。这项研究表明,尽管CB2在促进脾内GC和记忆B细胞的形成/维持方面发挥了作用,但它对T依赖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都是必不可少的。
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.
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