TACI is required for efficient plasma cell differentiation in response to T-Independent type 2 antigens
TACI is required for efficient plasma cell differentiation in response to T-Independent type 2 antigens
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DOI：
10.4049/jimmunol.179.4.2282
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发表时间：
2007-08-15
影响因子：
4.4
通讯作者：
Bram, Richard J.
中科院分区：
文献类型：
--
作者：
Mantchev, George T.;Cortesao, Catarina S.;Bram, Richard J.
微囊化微生物控制全身感染需要对细菌多糖的T-非依赖型11(TI-2)抗体反应。为了了解这种反应是如何演变的，我们探索了跨膜激活剂、钙调节剂和亲环素配体相互作用因子(TACI)的功能，TACI是TNFR家族的成员，是产生TI-2抗体所必需的。准单克隆(QM)小鼠对4-羟基-3-硝基苯乙酸酯(NP)-Ficoll产生强大的TI-2反应，这是由于脾边缘区NP特异性B细胞的高前体频率所致。在NP-Ficoll免疫后，与TACI阳性的QM小鼠相比，缺乏TACI的QM小鼠产生的NP特异性ASCs数量减少了2倍和1.6倍。我们的研究表明，TACI在激活之前起作用的时间较远，因为TACI在体外和体内对B细胞的激活和增殖都不是必需的。相反，缺乏TACI的QM B细胞比TACI熟练的QM细胞在细胞周期中停留的时间更长，并且对NP-Ficoll的反应损害了浆细胞的分化。我们认为TACI具有抑制B细胞持续增殖和刺激浆细胞分化的双重功能，从而解决了长期以来认为TACI可能同时具有B细胞抑制和刺激功能的悖论。通过在克隆扩增过程中更早地促进浆细胞分化，TACI可能会减少免疫球蛋白基因的体细胞超突变对T非依赖性AGS的应答而产生自身抗体的机会。
The control of systemic infection by encapsulated microorganisms requires T-independent type 11 (TI-2) Ab responses to bacterial polysaccharides. To understand how such responses evolve, we explored the function of transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI), a member of the TNFR family, required for TI-2 Ab production. Quasimonoclonal (QM) mice produce robust TI-2 responses to 4-hydroxy-3-nitrophenylacetate (NP)-Ficoll, owing to the high precursor frequency of NP-specific B cells in the marginal zone of the spleen. QM mice that lack TACI produce decreased numbers of IgM (2-fold) and IgG (1.6-fold) NP-specific ASCs, compared with TACI-positive QM mice in response to immunization with NP-Ficoll. Our studies indicate that TACI acts at a remote time from activation because TACI is not necessary for activation and proliferation of B cells both in vitro and in vivo. Instead, TACI-deficient QM B cells remained in the cell cycle longer than TACI-proficient QM cells and had impaired plasma cell differentiation in response to NP-Ficoll. We conclude that TACI has dual B cell-autonomous functions, inhibiting prolonged B cell proliferation and stimulating plasma cell differentiation, thus resolving the longstanding paradox that TACI may have both B cell-inhibitory and -stimulatory functions. By promoting plasma cell differentiation earlier during clonal expansion, TACI may decrease the chances of autoantibody production by somatic hypermutation of Ig genes in response to T-independent Ags.