Rationale B cells contribute to atherosclerosis through subset specific mechanisms. Whereas some controversy exists about the role of B-2 cells, B-1a cells are atheroprotective due to secretion of atheroprotective IgM antibodies independent of antigen. B-1b cells, a unique subset of B-1 cells that respond specifically to T cell-independent antigens, have not been studied within the context of atherosclerosis. Objective To determine whether B-1b cells produce atheroprotective IgM antibodies and function to protect against diet induced atherosclerosis. Methods and Results We demonstrate that B-1b cells are sufficient to produce IgM antibodies against oxidation specific epitopes (OSE) on LDL both in vitro and in vivo. Additionally, we demonstrate that B-1b cells provide atheroprotection after adoptive transfer into B and T cell deficient (Rag1−/−Apoe−/−) hosts. We implicate Id3 in the regulation of B-1b cells as B cell-specific Id3 knockout mice (Id3BKOApoe−/−) have increased numbers of B-1b cells systemically, increased titers of OSE-reactive IgM antibodies, and significantly reduced diet-induced atherosclerosis compared to Id3WTApoe−/− controls. Finally, we report that the presence of a homozygous SNP in ID3 in humans that attenuates Id3 function is associated with an increased percentage of circulating B-1 cells and anti-MDA-LDL IgM suggesting clinical relevance. Conclusions These results provide novel evidence that B-1b cells produce atheroprotective OSE-reactive IgM antibodies and protect against atherosclerosis in mice, and suggest that similar mechanisms may occur in humans.

Background Morbidity after gastrectomy remains high. The potentially modifiable risk factors have not been well described. This study considers a series of potentially modifiable patient-specific and perioperative characteristics that could be considered to reduce morbidity and mortality after gastrectomy. Methods This retrospective cohort study includes adults in the ACS NSQIP PUF dataset who underwent gastrectomy between 2011 and 2013. Sequential multivariable models were used to estimate effects of clinical covariates on study outcomes including morbidity, mortality, readmission and reoperation. Results 3,678 patients underwent gastrectomy. A majority of patients had distal gastrectomy (N= 2,799, 76.1%) and had resection for malignancy (N= 2,316, 63.0%). 798 patients (21.7%) experienced a major complication. Reoperation was required in 290 patients (7.9%). 30-day mortality was 5.2%. Age (OR=1.01, 95% CI: 1.01–1.02, p=0.001), preoperative malnutrition (OR=1.65, 95% CI: 1.35–2.02, p<0.001), total gastrectomy (OR=1.63, 95% CI: 1.31–2.03, p<0.001), benign indication for resection (OR=1.60, 95% CI: 1.29–1.97, p<0.001), blood transfusion (OR=2.57, 95% CI: 2.10–3.13, p<0.001), and intraoperative placement of a feeding tubes (OR=1.28, 95% CI: 1.00–1.62, p=0.047) were independently associated with increased risk of morbidity. Association between tobacco use and morbidity was statistically marginal (OR=1.23, 95% CI: 0.99–1.53, p=0.064). All-cause postoperative morbidity had significant associations with reoperation, readmission, and mortality (all p<0.001). Conclusions Mitigation of perioperative risk factors including smoking and malnutrition as well as identified operative considerations may improve outcomes after gastrectomy. Postoperative morbidity has the strongest association with other measures of poor outcome: reoperation, readmission, and mortality.

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