Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation

Follicular T-helper (TFH) cells cooperate with GL7+CD95+ germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for TFH cell differentiation and GC formation. After immunization with protein or infection with the protozoon Leishmania major, draining lymph nodes (LNs) of IFN-regulatory factor-4 (Irf4−/−) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyer’s patches of naive Irf4−/− mice. Accordingly, CD4+ T cells within the LNs and Peyer’s patches failed to express the TFH key transcription factor B-cell lymphoma-6 and other TFH-related molecules. During chronic leishmaniasis, the draining Irf4−/− LNs disappeared because of massive cell death. Adoptive transfer of WT CD4+ T cells or few L. major primed WT TFH cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity, Irf4−/− TFH cell differentiation was not rescued by close neighborhood to transferred WT TFH cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in the center of antibody production toward T-cell–dependent antigens

Estabilidade do reposicionamento anterior da maxila através de análise cefalométrica lateral Lateral cephalometric analysis of the stability of maxillary anterior repositioning

Este estudo cefalométrico retrospectivo foi proposto objetivando analisar a estabilidade do reposicionamento anterior da maxila, utilizando-se a osteotomia Le Fort I. A amostra consistiu de 30 telerradiografias de dez pacientes submetidos a um avanço cirúrgico da maxila, sem segmentação desta ou associação com qualquer cirurgia na mandíbula, realizado pela Área de Cirurgia Buco-Maxilo-Facial da Faculdade de Odontologia de Piracicaba - Unicamp. A mesma técnica de fixação interna rígida foi utilizada para todos os pacientes, e nenhum enxerto ou substituto ósseo foi usado. Três radiografias cefalométricas laterais foram realizadas para cada paciente, nos períodos pré e pós-operatórios imediatos, e com, no mínimo, seis meses após a cirurgia. Sobre estas radiografias foram feitas linhas de referência horizontal e vertical. Os pontos cefalométricos utilizados para calcular as mudanças de posição da maxila foram tanto esqueléticos, quanto dentários. A análise estatística (teste t de student pareado) não demonstrou diferença estatística significante entre os intervalos pós-operatórios imediato e com no mínimo seis meses. Concluímos que o reposicionamento anterior da maxila, utilizando-se a osteotomia Le Fort I, com fixação interna rígida e sem o uso de enxertos autógenos ou qualquer substituto ósseo, é um procedimento estável.<br>This is a retrospective cephalometric study designed to investigate the stability after anterior maxilla repositioning, by Le Fort I osteotomy. Thirty cephalometric radiographs were selected, from ten patients submitted to one-piece surgical maxillary advancement, with no concomitant mandibular surgery, performed by the Division of Oral and Maxillofacial Surgery of Piracicaba Dental School - Unicamp. These cases were submitted to the same internal rigid fixation technique, with no use of bone grafts or any bone substitute. Three lateral cephalometric radiographs were obtained for each patient, immediately presurgery and postsurgery, and at least six months after surgery. Lines were draw upon the X-rays to serve as horizontal and vertical reference lines.The landmarks used to measure maxillary positional changes consisted of skeletal and dental features. Statistical analysis (paired t student test) showed no significant differences between the immediately postsurgery and at least six months postsurgery periods. We concluded that the anterior maxillary repositioning by Le Fort I osteotomy, using rigid internal fixation, with no bone grafts or any bone substitute, is a stable procedure