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BAFF, a vital B cell survival and differentiation factor, has three receptors: B‐cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) and BR3. Although B cells are greatly reduced in B6.Baff−/− (which harbour no BAFF) and B6.Br3−/− mice (which harbour supra‐normal levels of BAFF), the distributions of B cell subsets and relationships between Foxp3+ and CD4+ cells in these mice differ. Using a large panel of B6 congenic knockout and/or transgenic mice, we demonstrate that (1) supra‐normal levels of BAFF per se do not explain the phenotypic differences between B6.Baff−/− and B6.Br3−/− mice; (2) B cells are expanded in B6.Taci−/− mice, with preferential expansion of follicular (FO) B cells at the expense of CD19+CD21−/loCD23−/lo B cells but without the preferential expansion of Foxp3+ cells observed in B6 mice bearing a Baff transgene; (3) despite no expansion in total B cells, percentages of FO B cells and marginal zone B cells are higher and percentages of CD19+CD21−/loCD23−/lo B cells are lower in young B6.Bcma−/− mice, consistent with the inability of B6.Br3−/−.Taci−/− mice to recapitulate the B cell profile of B6.Baff−/− mice; and (4) percentages of Foxp3+ cells in B6.Br3−/−.Taci−/− mice are intermediate between those in B6.Br3−/− and B6.Taci−/− mice despite the B cell profile of B6.Br3−/−.Taci−/− mice strongly resembling that of B6.Br3−/− mice. Collectively, our findings point to a non‐redundant role for each of the BAFF receptors in determining the ultimate lymphocyte profile of the host. This may have clinically relevant ramifications in that the degree that a candidate therapeutic agent blocks engagement of any given individual BAFF receptor may affect its clinical utility. [ABSTRACT FROM AUTHOR]

Objective: Heavy drinking poses serious risks to individuals with HIV, hepatitis C virus (HCV), and especially HIV/HCV coinfection. We adapted the National Institute on Alcohol Abuse and Alcoholism Clinician's Guide to address HIV/HCV coinfection and paired this with the "HealthCall" smartphone app to create an intervention tailored to HIV/HCV. After formative work and pretesting with HIV/HCV coinfected heavy drinkers, we conducted a pilot trial to determine potential of this new intervention for decreasing drinking. Method: A sample of 31 HIV/HCV coinfected heavy drinkers were randomly assigned to either intervention (n = 16) or control (n = 15; psychoeducation and brief advice) conditions. All participants completed a 60-day program consisting of approximately 25-minute-long baseline sessions and brief 5-10-minute booster sessions at 30 and 60 days, as well as an assessment-only follow-up at 90 days. Outcomes were measured using the Timeline Followback at baseline, 30, 60, and 90 days. Generalized linear models were used for analysis. Results: Intervention participants drank fewer mean drinks per drinking day at 60 days (incidence rate ratio [IRR] = 0.43, p = .03) and 90 days (IRR = 0.34, p < .01). Intervention participants also reported fewer drinking days at 90 days (mean difference = 34.5%; p < .01). Self-efficacy differed between groups during intervention (p < .05). Conclusions: Although our sample was small, our results suggested lower drinking among participants who received a modified Clinician's Guide intervention plus use of the smartphone app HealthCall, in comparison with education and advice alone. A larger study is indicated to further examine this brief, disseminable intervention for HIV/HCV coinfected drinkers. [ABSTRACT FROM AUTHOR]

Objective: We assessed the contributions of B cell and T cell subsets to the disparate clinical outcomes in NZM.Baff -/- and NZM.Br3 -/- mice., Methods: We assessed in NZM wild-type, NZM.Baff -/- , and NZM.Br3 -/- mice numbers and percentages of B cells and subsets, T cells and subsets, and in vivo proliferation and survival of forkhead box P3 (Foxp3) + cells by fluorescence-activated cell sorting. Relationships between percentages of Foxp3 + cells and numbers of CD19 + and CD4 + cells were assessed by linear regressions., Results: In each age and sex cohort, percentages and numbers of CD19 + cells were similar in NZM.Baff -/- and NZM.Br3 -/- mice. Percentages of CD3 + and CD4 + cells were greater in NZM.Br3 -/- than in NZM.Baff -/- mice, with the CD4 to CD3 cell ratios being greater in NZM.Br3 -/- than in NZM.Baff -/- mice and percentages of Foxp3 + cells in NZM.Br3 -/- mice being lower than in NZM.Baff -/- mice. Percentages of Foxp3 + cells correlated positively with CD19 + cells in NZM.Baff -/- mice but negatively in NZM.Br3 -/- mice. In vivo proliferation and survival of Foxp3 + cells were lower in NZM.Baff -/- mice than in NZM.Br3 -/- mice., Conclusion: Differences between NZM.Baff -/- and NZM.Br3 -/- mice in Foxp3 + cells and their relationships with CD19 + cells may have more to do with their divergent clinical outcomes than do differences in numbers of B cells. These unexpected findings suggest that B cell activating factor (BAFF)-B cell maturation antigen (BCMA) or BAFF-Transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) interactions may help drive development of clinical systemic lupus erythematosus (SLE) even under conditions of considerable B cell depletion. Insufficient blocking of BAFF-BCMA and BAFF-TACI interactions may lie at the heart of incomplete clinical response to BAFF-targeting agents in human SLE., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)