Chronic viral infections impaired the growth process of splenic B cells by upregulating Bbc3 and Atf3 in LCMV-CL13 infected mouse model.

Chronic persistent viral infections can lead to significant spleen damage, thus disrupting the host humoral immune response; however, the underlying mechanisms remain unclear. In this study, we employed a Lymphocytic choriomeningitis virus (LCMV) chronic infection model to investigate the effects of virus infection on spleen damage. Mice infected with Lymphocytic choriomeningitis virus clone 13 (LCMV-CL13) presented a series of pathological features, such as white pulp atrophy and reduced germinal center diameter, length, and area in the spleen. More importantly, we observed a diminished GC response alongside a weak antibody response in the chronic infection model. Single-cell RNA sequencing (scRNA-seq) further revealed the dysregulation of gene expression, including Bbc3, Atf3, and Ptpn6, which inhibit B-cell differentiation during chronic viral infection. We verify that the upregulation of Bbc3 or Atf3, respectively, can promote apoptosis in BaF3 cells. Immune repertoire (IR) analysis revealed that the molecular diversity of the BCR repertoire after LCMV-CL13 infection, specifically manifested in BCR clonal diversity, IGHV gene segment usage preference, and CDR3 sequence changes. In conclusion, this study demonstrated that chronic LCMV-CL13 infection interrupted the development of splenic B cells by increasing the expression of apoptosis genes, thus enhancing our understanding of the underlying mechanisms of B-cell development interruption during chronic viral infection.