Communication between CD4 T cells and cognate B cells is key for the former to fully mature into germinal center–T follicular helper (GC-T FH ) cells and for the latter to mount a CD4 T cell–dependent humoral immune response. Although this interaction occurs in a B:T synapse–dependent manner, how CD4 T cells transcriptionally regulate B:T synapse formation remains largely unknown. Here, we report that Mef2d, an isoform of the myocyte enhancer factor 2 (Mef2) transcription factor family, is a critical regulator of this process. In CD4 T cells, Mef2d negatively regulates expression of Sh2d1a , which encodes SLAM-associated protein (SAP), a critical regulator of B:T synapses. We found that Mef2d regulates Sh2d1a expression via DNA binding–dependent transcriptional repression, inhibiting SAP-dependent B:T synapse formation and preventing antigen-specific CD4 T cells from differentiating into GC-T FH cells. Mef2d also impeded IL-21 production by CD4 T cells, an important B cell help signaling molecule, via direct repression of the Il21 gene. In contrast, CD4 T cell–specific disruption of Mef2d led to a substantial increase in GC-T FH differentiation in response to protein immunization, concurrent with enhanced SAP expression. MEF2D mRNA expression inversely correlates with human systemic lupus erythematosus (SLE) patient autoimmune parameters, including circulating T FH –like cell frequencies, autoantibodies, and SLEDAI scores. These findings highlight Mef2d as a pivotal rheostat in CD4 T cells for controlling GC formation and antibody production by B cells.
Variation of female and male strobilus production among clones over 4 consecutive years was estimated, and genetic variance, heritability, and genetic correlation in strobilus production were investigated in the second-generation seed orchard of Pinus thunbergii. This seed orchard was created with grafts selected according to the volume growth of their offspring. The production of female strobili continued to increase, whereas the production of male strobili fluctuated throughout the investigated period. The number of female strobili was highest in rich cone years, but the production of male strobili was not the same in rich or poor years. The maleness index showed a balance between female and male parents that occurred when male strobilus production was in rich or poor years. The parental balance curve for female strobilus production was closer to the expectation (i.e., more equal contribution) than that for male strobilus production in all years. The analysis of variance revealed significant differences among clones in female and male strobilus production over the four-year period. The narrow-sense heritability was higher in male strobilus production than female strobilus, implying that male strobilus production was under genetic control. The Pearson’s correlation was positive and mostly significant, indicating that female strobilus production was reflected in male strobilus production. The effective parent number was lowest in moderate and good years for cone production. The loss of gene diversity in seed crops was lower than expected based on clonal fertility variation.
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