Indiana University-Purdue University Indianapolis (IUPUI) / Germinal Centers (GCs) are transient lymphoid structures that arise in lymphoid organs in response to T cell-dependent antigen. Within the GC, follicular T helper (TFH) cells promote GC B cell differentiation and in turn the proper antibody production to protect us from invading pathogens. We wished to study the regulation of this process by transcription factors STAT3 and Bcl6. STAT3 is important for both TFH cell differentiation and IL-4 production by Th2 cells. IL-4 is a major functional cytokine produced by TFH cells. To dissect the role of STAT3 in IL-4 production by TFH cells, we generated T cell-specific conditional STAT3 knockout mice (STAT3KO). Compared to WT mice, TFH cell differentiation in STAT3KO mice was partially impaired, both in spleen following sheep red blood cells (SRBC) immunization and in Peyer's patches (PPs). In STAT3KO mice, the numbers of splenic GC B cells were markedly decreased, whereas PP GC B cells developed at normal numbers and IgG1 class switching was greatly increased. Unexpectedly, we found that STAT3 intrinsically suppressed the expression of IL-4 and Bcl6 in TFH cells. Mechanistically, in vitro repression of IL-4 expression in CD4 T cells by Bcl6 required STAT3 function. Apart from TFH cells, the GC reaction is also controlled by regulatory follicular T helper (TFR) cells, a subset of Treg cells. To study the mechanism of how TFR cells regulate the GC reaction, we generated mice specifically lacking TFR cells by specifically deleting Bcl6 in Treg cells. Following immunization, these "Bcl6FC" mice developed normal TFH and GC B cell populations. However, Bcl6FC mice produced altered antigen-specific antibody responses, with reduced titers of IgG and increased IgA. Bcl6FC mice also developed IgG antibodies with significantly decreased avidity to antigen in an HIV-1 gp120 "prime-boost" vaccine model. Additionally, TFH cells from Bcl6FC mice produced higher levels of Interferon-γ, IL-10 and IL-21. Loss of TFR cells therefore leads to highly abnormal TFH and GC B cell responses. Overall, our studies have uncovered unexpected regulatory roles of STAT3 in TFH cell function as well as the novel regulatory roles of TFR cells on cytokine production by TFH cells and on antibody production.

HP, uma bactéria gram-negativa envolvida na patogênese do tecido gastroduodenal, foi classificada como carcinogênico classe I em 1994. Seus mecanismos são pouco entendidos, mas a presença da ilha de patogenicidade (PAI) é fator importante de virulência. PAI sugere aumento da proliferação celular, diminuindo a apoptose. A detecção do HP e da PAI (cagA) foi feita por PCR. Casos positivos são associados aos resultados histopatológicos, proliferação celular e apoptose. Detectamos HP em 37,0% (111/300), sendo 40,5% (45/111) dos pacientes cagA+. A relação proliferação celular/apoptose (P/A) mostra aumento em pacientes infectados por HP/cagA até 8,8 vezes maior no surgimento de doença gástrica grave / HP, a gram-negative bacterium involved in pathogenesis of gastroduodenal tissues, was classified as type I carcinogen in 1994. The mechanisms involved in carcinogenesis point to the pathogenicity island (PAI) as an important virulent factor. PAI suggests an increase in cell proliferation, attenuating apoptosis. HP detection and PAI were performed by using PCR. Positive results were associated to the histological findings, cell proliferation and apoptosis. We detected HP in 37,0% (111/300) and 40,5% (45/111) of the patients. A significant increase index appears between proliferation and apoptosis in those infected by HP/cagA+ with higher risk of 8,8 for the development of gastric cancer

HP, uma bactéria gram-negativa envolvida na patogênese do tecido gastroduodenal, foi classificada como carcinogênico classe I em 1994. Seus mecanismos são pouco entendidos, mas a presença da ilha de patogenicidade (PAI) é fator importante de virulência. PAI sugere aumento da proliferação celular, diminuindo a apoptose. A detecção do HP e da PAI (cagA) foi feita por PCR. Casos positivos são associados aos resultados histopatológicos, proliferação celular e apoptose. Detectamos HP em 37,0% (111/300), sendo 40,5% (45/111) dos pacientes cagA+. A relação proliferação celular/apoptose (P/A) mostra aumento em pacientes infectados por HP/cagA até 8,8 vezes maior no surgimento de doença gástrica grave / HP, a gram-negative bacterium involved in pathogenesis of gastroduodenal tissues, was classified as type I carcinogen in 1994. The mechanisms involved in carcinogenesis point to the pathogenicity island (PAI) as an important virulent factor. PAI suggests an increase in cell proliferation, attenuating apoptosis. HP detection and PAI were performed by using PCR. Positive results were associated to the histological findings, cell proliferation and apoptosis. We detected HP in 37,0% (111/300) and 40,5% (45/111) of the patients. A significant increase index appears between proliferation and apoptosis in those infected by HP/cagA+ with higher risk of 8,8 for the development of gastric cancer