Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (B RM ) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza - specific B RM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)– and nucleoprotein (NP)–specific lung B RM . We found that CCR6 facilitates increased recruitment and/or retention of B RM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning B RM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that B RM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.

Debate still exists for the management of choledocholithiasis. The purpose of this study is to quantify the rate of recurrent choledocholithiasis post choledochoscopic bile duct exploration (CBDE) in comparison to ERCP and sphincterotomy, and to demonstrate the feasibility of this approach in a busy metropolitan hospital. Data of patients undergoing CBDE from 2009–2014 at the Northern Hospital, Victoria, Australia, was collected retrospectively. Primary outcomes were bile duct clearance rate and rate of recurrent stones post-clearance. Secondary outcomes measured were post-operative complications, laparoscopic to open conversion rate and operative time. Data of patients undergoing ERCP at the same institution was collected and compared. In total, there were 4,091 cholecystectomy cases performed from 2009–2014, of which 260 (6.3%) of patients had an intraoperative cholangiography (IOC) indicating a common bile duct (CBD) stone. Two hundred and forty-eight patients (95.3%) had a CBDE. The remaining 12 patients (4.6%) had radiological clearance, which were excluded from the study. The overall clearance rate for patients undergoing CBDE was 84% (209/248). The risk of recurrent stones up to 8 years post clearance was 2% (4/209). In the same institution, and between 1998–2012, a total of 1,148 patients underwent ERCP, of which 571 had endoscopic sphincterotomy (ES). Forty-three patients required a repeat ERCP for recurrent CBD stones with a complication rate of 7.5%. Time to recurrence ranged from 6 months to 10 years with a mean of 4.5 years. The rate of recurrence was lower in the CBDE group compared to the patients who had an ERCP (8.9% vs. 2%). CBDE is a feasible and effective method for clearance of CBD stones at the time of laparoscopic cholecystectomy. This approach, although not widely used, reduces the need for ERCP, which has inherent complications. In the longer term, this series showed a significant reduction in the rate of CBD stone recurrence.

Endemic human coronaviruses (hCoV) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T cell memory in adults. We quantified CD4 T cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2 uninfected individuals. T cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung draining lymph nodes. Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.

Objectives. Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults. Methods. We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals. Antigen-specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation-induced marker assay and characterised for memory phenotype and chemokine receptor expression. Results. T-cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6 + central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung-draining lymph nodes. Conclusion. Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.

Level-two cohort study.