RESUMO
The role of TLR4 in mature B cell activation is well characterized. However, little is known about TLR4 role in B cell development. Here, we analyzed the effects of TLR4 and TLR2 agonists on B cell development using an in vitro model of B cell maturation. Highly purified B220(+)IgM(-) B cell precursors from normal C57BL/6 mouse were cultured for 72 h, and B cell maturation in the presence of the TLR agonists was evaluated by expression of IgM, IgD, CD23, and AA4. The addition of LPS or lipid A resulted in a marked increase in the percentage of CD23(+) B cells, while Pam3Cys had no effect alone, but inhibited the increase of CD23(+) B cell population induced by lipid A or LPS. The TLR4-induced expression of CD23 is not accompanied by full activation of the lymphocyte, as suggested by the absence of activation Ag CD69. Experiments with TLR2-knockout mice confirmed that the inhibitory effects of Pam3Cys depend on the expression of TLR2. We studied the effects of TLR-agonists on early steps of B cell differentiation by analyzing IL-7 responsiveness and phenotype of early B cell precursors: we found that both lipid A and Pam3Cys impaired IL-7-dependent proliferation; however, while lipid A up-regulates B220 surface marker, consistent with a more mature phenotype of the IgM(-) precursors, Pam3Cys keeps the precursors on a more immature stage. Taken together, our results suggest that TLR4 signaling favors B lymphocyte maturation, whereas TLR2 arrests/retards that process, ascribing new roles for TLRs in B cell physiology.
Assuntos
Linfócitos B/citologia , Linfócitos B/imunologia , Diferenciação Celular/imunologia , Cisteína/análogos & derivados , Inibidores do Crescimento/fisiologia , Receptores Imunológicos/fisiologia , Transdução de Sinais/imunologia , Animais , Linfócitos B/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Cisteína/antagonistas & inibidores , Cisteína/farmacologia , Inibidores do Crescimento/agonistas , Inibidores do Crescimento/deficiência , Inibidores do Crescimento/metabolismo , Imunofenotipagem , Ligantes , Lipoproteínas/antagonistas & inibidores , Lipoproteínas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Imunológicos/agonistas , Receptores Imunológicos/deficiência , Receptores Imunológicos/metabolismo , Transdução de Sinais/genética , Células-Tronco/citologia , Células-Tronco/imunologia , Células-Tronco/metabolismo , Receptor 2 Toll-Like , Receptor 4 Toll-LikeRESUMO
The persistent müllerian duct syndrome represents a rare form of male pseudohermaphroditism secondary to anti-müllerian hormone deficiency. We describe 2 cases of phenotypically male postpubertal patients with a uterus and tubes. Both patients presented with bilateral cryptorchidism, 1 was seen for gynecomastia and 1 was seen for an abdominal mass that was found to be a testicular tumor.