KSHV induces immunoglobulin rearrangements in mature B lymphocytes.

ABSTRACT: Kaposi sarcoma herpesvirus (KSHV/HHV-8) is a B cell tropic human pathogen, which is present in vivo in monotypic immunoglobulin ? (Ig?) light chain but polyclonal B cells. In the current study, we use cell sorting to infect specific B cell lineages from human tonsil specimens in order to examine the immunophenotypic alterations associated with KSHV infection. We describe IL-6 dependent maturation of naïve B lymphocytes in response to KSHV infection and determine that the Ig? monotypic bias of KSHV infection in vivo is due to viral induction of BCR revision. Infection of immunoglobulin ? (Ig?) naïve B cells induces expression of Ig? and isotypic inclusion, with eventual loss of Ig?. We show that this phenotypic shift occurs via re-induction of Rag-mediated V(D)J recombination. These data explain the selective presence of KSHV in Ig? B cells in vivo and provide the first evidence that a human pathogen can manipulate the molecular mechanisms responsible for immunoglobulin diversity.

SUBMITTER: Totonchy J 

PROVIDER: S-EPMC5919685 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature