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• • Slc7a5 knockdown results in 34 differentially regulated genes. • • B1a but not B2 cells are depleted when Slc7a5 is knocked down in adult mice. • • Slc7a5-deficient bone marrow B1a cells fail to develop due to dysregulation of the mTOR signaling pathway. Slc7a5 is an important amino acid transporter that is highly expressed in metabolically active and rapidly proliferating cells. To explore the effect of Slc7a5 on adult B cell development, we conditionally deleted Slc7a5 in murine B cells and observed a significant reduction of B1a cells. In contrast to PI3K-Akt pathway activation, activity of the mTOR pathway was decreased. This may result from intracellular amino acid starvation in Slc7a5 knockdown (Slc7a5 KD) bone marrow B cells, thereby dampening B1a development. RNA-seq analysis demonstrated increased translation and reduced proliferation in Slc7a5 KD bone marrow B cells. Overall, the results of our study highlight the importance of Slc7a5 in peritoneal B1a cell development. [ABSTRACT FROM AUTHOR]

As a major cellular component in tumor microenvironment, the distribution, frequency, and prognostic significance of infiltrating B cell subsets in hepatocellular carcinoma (HCC) remain controversial. Using tyramide signal amplification (TSA) based fluorescent multiplexed immunohistochemistry in situ, we evaluated the distribution and frequency of B cell subsets in two independent HCC cohorts (n = 619). The results were further confirmed by flow cytometry. Correlations of B cell subsets with clinicopathologic features and patient prognosis were analyzed. Five B cell subsets were defined by multiplexed immunohistochemistry and each subset was clearly separated by t-SNE dimension reduction analysis. Notably, the densities of all B cell subsets were significantly decreased in the tumor. The frequency of plasma cells within B cells was most abundant in the tumor. In training cohort (n = 258), high densities of tumor-infiltrating CD20+ B cells, naive B cells, IgM+ memory B cells, CD27− isotype-switched memory B cells, and plasma cells were associated with superior survival. Multivariate analysis further identified CD20+ B cells, naive B cells, and CD27− isotype-switched memory B cells as independent prognosticators for survival. Unsupervised cluster analysis confirmed increased B cell subsets harbored superior survival. In addition, high density of B cells was correlated with smaller tumor size and well differentiation. The results were validated in the independent cohort of 361 HCC patients. Intratumor infiltration of B cells is significantly impaired during HCC progression. High densities of tumor-infiltrating B cells imply a better clinical outcome. Therapies designed to target B cells may be a novel strategy in HCC. [ABSTRACT FROM AUTHOR]