BANK1 interacts with TRAF6 and MyD88 in innate immune signaling in B cells

Evidence supports a possible role of BANK1 in innate immune signaling in B cells. In the present study, we investigated the interaction of BANK1 with two key mediators in interferon and inflammatory cytokine production, TRAF6 and MyD88. We revealed by coimmunoprecipitation (CoIP) analyses the binding of BANK1 with TRAF6 and MyD88, which were mediated by the BANK1 Toll/interleukin-1 receptor (TIR) domain. In addition, the natural BANK1-40C variant showed increased binding to MyD88. Next, we demonstrated in mouse splenic B cells that BANK1 colocalized with Toll-like receptor (TLR) 7 and TLR9 and that after stimulation with TLR7 and TLR9 agonists, the number of double-positive BANK1-TLR7, -TLR9, -TRAF6, and -MyD88 cells increased. Furthermore, we identified five TRAF6-binding motifs (BMs) in BANK1 and confirmed by point mutations and decoy peptide experiments that the C-terminal domain of BANK1-full-length (-FL) and the N-terminal domain of BANK1-Delta2 (-D2) are necessary for this binding. Functionally, we determined that the absence of the TIR domain in BANK1-D2 is important for its lysine (K)63-linked polyubiquitination and its ability to produce interleukin (IL)-8. Overall, our study describes a specific function of BANK1 in MyD88-TRAF6 innate immune signaling in B cells, clarifies functional differences between the two BANK1 isoforms and explains for the first time a functional link between autoimmune phenotypes including SLE and the naturally occurring BANK1-40C variant

Ecological Contexts in Adolescent Pregnancy: The Role of Individual, Sociodemographic, Familial and Relational Variables in Understanding Risk of Occurrence and Adjustment Patterns

Adolescent pregnancy appears today as an intricate tapestry where different dimensions interact. In our study we examined the associations between individual, sociodemographic, familial, and relational variables and their impact in the occurrence of pregnancy and adolescents’ adjustment to it. Participants were Portuguese pregnant and non-pregnant adolescents (N = 833). Ecological contexts were characterized, and individual and relational adjustment (depressive symptoms and quality of life; perceived quality of relationship with significant others – parents, romantic partner and friends) were evaluated. Differences between the ecologies of adolescents in both groups were identified. Familial and relational variables were significantly associated with both the risk of pregnancy and more difficulties in adjustment. Implications for preventive intervention are discussed