Search

We have deliberately targeted collaboration between T cells and certain B cells by using a heteroconjugate (HETCONJ) antibody. This specific reagent was created by cross-linking the F(ab')2 portions of and-I-Ab and ant)-CD3 monoclonal antibodies. Spleen cells from B6 (I-Ab) but not bm 12 (I-A'bm12) mice proliferated in vitro in the presence of the HETCONJ. Similarly. T-cell dependent IgM secretion was induced in B cells from B6, yet only weakly in B cells from bm12 mice. Using B cells from Igh allotype double congenic (B6.C20 Igha/I-Ab and bm12, Ighb/I-Abm12) mice in co-culture experiments, we have used the HETCONJ to study linked versus bystander T--B interaction. B-cell activation, mediated by HETCONJ, was 10 times greater in unseparated than in resting splenic B cells. T--B interaction through T--B contact was more efficient than activation through bystander effects both for unseparated and resting splenic B cells. Large, already activated B cells, in contrast, did not show a preference for linked recognition. Our reagent has mimicked some of the events involved in T--B collaboration and may be useful in studying the molecular basis of cellular interactions. [ABSTRACT FROM AUTHOR]

Importance: Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited., Objective: To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD)., Design, Setting, and Participants: This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024., Exposures: Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks' gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed., Main Outcomes and Measures: Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings., Results: The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85)., Conclusions and Relevance: In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.