Central nervous system (CNS) infection with neurotropic West Nile virus (WNV), triggers infiltration of pathogenic bone marrow (BM)-derived monocytes, accompanied by enhanced monopoiesis, culminating in seizures and lethal immunopathology. These are absent in asymptomatic WNV-infected mice, which nevertheless become immune. While antibodies are crucial to WNV immunity, little is known about haematopoietic B cell responses during encephalitis. B cell progenitor depletion occurs during systemic murine influenza virus infection, but we have also shown this in WNV encephalitis, where infection is limited to the CNS. Using an 18-parameter immunophenotyping panel, detailed subset analysis revealed that while all B cell subtypes in the BM decreased by d7 post infection (p.i.), the largest decreases were in the early phenotypes, pro-, pre-, immature and transitional B cells. Additionally, B cell progenitors decreased in the blood between d6 and d7 p.i., but increased in the cervical lymph nodes over this time. We found that the decrease in BM B cells was due to decreased proliferation of the normally highly proliferating pro- and pre-B cells, as shown by reduced incorporation of 5-bromo-2'-deoxyuridine (BrdU), but not due to apoptosis, as shown by a lack of Annexin V staining. Interestingly, in mock-infected mice, pro-, pre-, immature and transitional B cells adoptively transferred 48 h prior to harvest preferentially homed to bone marrow, while both early and late subtypes homed to the spleen, and late mature B cells homed to the inguinal lymph nodes. Interestingly, a similar reduction occurs in B cell progenitor subsets during acute infection with Zika virus, lymphocytic choriomeningitis virus (LCMV), and cerebral malaria, with a minor reduction in mature subsets, suggesting similar developmental B cell modulation in various inflammatory conditions. This provides a platform for future targeted immunomodulatory therapies.