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The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5+ DCs are an essential component of optimal ICB therapy.

Objective: To investigate the clinical characteristics and treatment of relapsed CD5 + diffuse large B-cell lymphoma (DLBCL)., Methods: The data of a patient with CD5 + DLBCL was collected, and its clinical characteristics and treatment outcome were analyzed., Results: The patient developed hemophagocytic syndrome and achieved complete remission (CR) after 6 cycles of R-ECHOP chemotherapy, then relapsed. After 2 cycles of PD-1 inhibitor combined with lenalidomide treatment, the patient achieved CR again accompanied by a decrease of interleukin (IL)-10 expression level. After a total of 15 cycles of chemotherapy, the patient remained in CR for 24 months, and the level of IL-10 remained in the normal range., Conclusion: PD-1 inhibitor combined with lenalidomide regimen may be a new treatment for relapsed CD5 + DLBCL.

Introduction: Natural antibody (NAb) derived from CD5+ B-1 cells maintains tissue homeostasis, controls inflammation, aids in establishing long-term protective responses against pathogens, and provides immediate protection from infection. CD5+ B-1 cell NAbs recognize evolutionarily fixed epitopes, such as phosphatidylcholine (PtC), found on bacteria and senescent red blood cells. Anti-PtC antibodies are essential in protection against bacterial sepsis. CD5+ B-1 cell-derived NAbs have a unique germline-like structure that lacks N-additions, a feature critical for providing protection against infection. Previously, we demonstrated the repertoire and germline status of PtC+CD5+ B-1 cell IgM obtained from male mice changes with age depending on the anatomical location of the B-1 cells. More recently, we demonstrated serum antibody from aged female mice maintains protection against pneumococcal infection, whereas serum antibody from male mice does not provide protection., Results: Here, we show that aged female mice have significantly more splenic PtC+CD5+ B-1 cells and more PtC specific serum IgM than aged male mice. Furthermore, we find both age and biological sex related repertoire differences when comparing B cell receptor (BCR) sequencing results of PtC+CD5+ B-1 cells. While BCR germline status of PtC+CD5+ B-1 cells from aged male and female mice is similar in the peritoneal cavity, it differs significantly in the spleen, where aged females retain germline configuration and aged males do not. Nucleic acid sensing toll-like receptors are critical in the maintenance of PtC+ B-1 cells; therefore, to begin to understand the mechanism of differences observed between the male and female PtC+CD5+ B-1 cell repertoire, we analyzed levels of cell-free nucleic acids and found increases in aged females., Conclusion: Our results suggest the antigenic milieu differs between aged males and females, leading to differential selection of antigen-specific B-1 cells over time. Further elucidation of how biological sex differences influence the maintenance of B-1 cells within the aging environment will be essential to understand sex and age-related disparities in the susceptibility to bacterial infection and will aid in the development of more effective vaccination and/or therapeutic strategies specific for males and females., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Webster, Tsuji, Clemente and Holodick.)

Background: The view of prostate cancer (PCa) progression as a result of the interaction of epithelial cancer cells with the host's immune system is supported by the presence of tumor infiltrating lymphocytes (TILs). TILs fate and interaction with the tumor microenvironment is mediated by accessory molecules such as CD5 and CD6, two signal-transducing coreceptors involved in fine-tuning of T cell responses. While the nature of the CD5 ligand is still controversial, CD6 binds CD166/ALCAM, a cell adhesion molecule involved in progression and dissemination of epithelial cancers, including PCa. The purpose of the present study was to determine the role of CD5, CD6, and CD166/ALCAM gene variants in PCa., Methods: Functionally relevant CD5 (rs2241002 and rs2229177), CD6 (rs17824933, rs11230563, and rs12360861) and CD166/ALCAM (rs6437585, rs579565, rs1044243, and rs35271455) single nucleotide polymorphisms (SNPs) were genotyped in germline DNA samples from 376 PCa patients. Their association with PCa prognostic factors, namely biochemical recurrence (BCR) and International Society of Urological Pathology (ISUP) grade was analyzed by generalized linear models and survival analyses., Result: Proportional hazards regression showed that the minor CD6 rs12360861 AA and CD166/ALCAM rs579565 AA genotypes were associated with earlier BCR, with hazard ratios of 2.65 (95% CI: 1.39-5.05, p = 0.003) and 1.86, (95% CI: 1.02-3.39, p = 0.043), respectively. Individually, none of the analyzed SNPs was significantly associated with ISUP grade, but haplotype analyses revealed association of the CD5 rs2241002 C -rs2229177 T haplotype with ISUP grade ≥2, with odds ratio of 1.52 (95% CI: 1.05-2.21, p = 0.026)., Conclusion: The results show the impact on PCa aggressiveness and recurrence brought about by gene variants involved in modulation of lymphocyte activation (CD5, CD6) and immune-epithelial cell adhesion (CD166/ALCAM) in PCa aggressiveness and recurrence, thus supporting a role for host immune response in PCa pathophysiology., (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

CD5 is constitutively expressed on all T cells and is a negative regulator of lymphocyte function. However, the full extent of CD5 function in immunity remains unclear. CD5 deficiency impacts thymic selection and extra-thymic regulatory T cell generation, yet CD5 knockout was reported to cause no immune pathology. Here we show that CD5 is a key modulator of gut immunity. We generated mice with inducible CD5 knockdown (KD) in the autoimmune-prone nonobese diabetic (NOD) background. CD5 deficiency caused T cell-dependent wasting disease driven by chronic gut immune dysregulation. CD5 inhibition also exacerbated acute experimental colitis. Mechanistically, loss of CD5 increased phospho-Stat3 levels, leading to elevated IL-17A secretion. Our data reveal a new facet of CD5 function in shaping the T cell cytokine profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schuster, Kiaf, Hatzihristidis, Ruckdeschel, Nieves-Bonilla, Ishikawa, Zhao, Zheng, Love and Kissler.)

We reported 46 cases of Diffuse Large B-cell lymphoma which abnormally expressed CD5 protein (De Novo CD5-positive DLBCL), which had attracted researcher's attention for a period of time for its poor prognosis. However, there were few studies on its molecular change. In the present article, we summarized the genetic alterations using a lymphopanel detection method by Next Generation Sequencing(NGS). The most frequently mutated genes were MYD88 L265P (20/46, 43.5%), followed by PIMI (19/46, 41.3%), IGLL5 (13/46, 28.3%)and CD79B (11/46, 23.9%). We further investigated the relationship between gene alterations and prognosis using OS(Overall survival) and PFS(Progression-free survival). MYD88, CREBBP, and ACTB mutation were significantly associated with inferior OS (P = 0.032, 0.000, 0.001), PIMI, CREBBP, ACTB and CXCR4 mutation were significantly associated with inferior PFS (P = 0.016, 0.001, 0.045, 0.024). Meanwhile, we found that De Novo CD5-positive DLBCL had BCL-6(9/46,19.6%), C-MYC (4/46, 8.7%) and IRF4 (2/19, 10.5%) rearrangement, but without BCL-2 rearrangement, there were no significantly associations with prognosis. In summary, our research explored the gene alterations of De Novo CD5-positive DLBCL in a relatively large scale for the first time, the most common gene mutation was MYD88 L265P which was also a potential prognostic factor, providing a potential therapeutic target for the patients of De Novo CD5-positive DLBCL., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Natural Abs are primarily produced by B-1 cells and are essential for protection against Streptococcus pneumoniae The incidence and mortality rate for pneumococcal infection increases dramatically after age 65, disproportionately affecting males in both human and murine systems. To date, there is a significant gap in our understanding of the relationship among sex, aging, natural IgM efficacy, and the natural IgM repertoire. Our investigation demonstrates that the protective capacity of serum IgM against pneumococcal infection is maintained in IgM obtained from aged female mice but absent in IgM from aged male mice. To understand this difference in protective capacity, we examined serum Ig, discovering that the protective change was not associated with shifts in levels of phosphorylcholine (PC)- or pneumococcal capsular polysaccharide serotype 3-specific IgM. Interestingly, we observed that aged females have an increase in the total number of CD5 + B-1 cells, higher serum IL-5 levels, and a larger percentage of aged female CD5 + B-1 cells that express CD86 as compared with aged males. Furthermore, single-cell IgM repertoire analysis from peritoneal PC + , splenic PC + , and bone marrow CD5 + B-1 cell subsets demonstrated greater diversity with age and a higher level of germline status in female mice than previously observed in studies of aged male mice. Aged female CD5 + B-1 cells also expressed higher levels of transcripts associated with cell activity and self-renewal, such as Nanog and Hmga2 Taken together, these data indicate that females maintain a more diverse and active CD5 + B-1 cell pool and natural IgM repertoire, which has implications for sex-related susceptibility to infection and disease., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Objective: Several studies indicated that tonsillectomy can improve the prognosis of patients with immunoglobulin A nephropathy (IgAN). However, the relationship between tonsillar immunity and IgAN is still unclear., Methods: A total of 14 IgAN patients were recruited in the current study from May 2015 to April 2016 in Tongji Hospital. B cells, dendritic cells (DCs), and IgA1 positive cells in human tonsils were detected using immunofluorescence and immunohistochemistry. Correlations between these cells and clinicopathologic features were evaluated., Results: CD19 + CD5 + B cells were predominantly located in germinal centers and mantle zones of lymphoid follicles, the CD208+ DCs were distributed in the interfollicular and subepithelial area, and IgA1-positive cells were predominantly detected in mantle zones of lymphoid follicles and subepithelial tissues. The numbers of CD19 + CD5 + B cells, CD208 + DCs, and IgA1-positive cells in tonsillar tissues from IgAN patients were significantly higher than those in the normal controls (P<0.01, respectively). CD19 + CD5 + B cells, CD208 + DCs, and IgA1-positive cells in tonsillar tissues were significantly associated with 24-h proteinuria levels and tubular atrophy/interstitial fibrosis of IgAN., Conclusion: CD19 + CD5 + B cells, CD208 + DCs, and IgA1-positive cells in tonsillar tissues might be involved in the pathogenesis of IgAN., (© 2022. Huazhong University of Science and Technology.)