Specific susceptibility of sensitized (memory) B cells to suppression and antigenic alteration by murine leukemia virus

Abstract

Mice infected with murine oncogenic RNA viruses, either Friend virus (FV) or Moloney leukemia virus (MuLV-M) reacted well to a primary immunization with antigen(s) of Vibrio cholerae; both the kinetics and magnitude of the direct (IgM) primary vibriolytic antibody plaque forming cell (PFC) response in the spleen was the same as in non-infected control mice. In contrast, the anamnestic PFC (IgM) response of mice preimmunized with cholera and later (2 to 9 months following priming) infected with either FV or MuLV-M, before the secondary challenge, was inhibited 90% or more when compared to the anamnestic response of controls. Hemolytic PFC response to a single (primary) immunization with sheep red blood cells (sRBC, an antigen to which laboratory mice have a natural immune background) was suppressed by infection with both viruses in a manner similar to the suppression of the secondary vibiolytic response. The suppressive effect of FV, and the lack of it, on these different immune responses was correlated with the appearance of FV-induced cell membrane antigen, FVMA, on respective individual PFC from the spleen. FVMA was detected by inhibition of PFC in the presence of specific antiserum, anti-FVMA, and complement (C). In particular, about 80% of the FV-infected mice with an anamnestic response to a secondary challenge with cholera antigen had a significant decline in the proportion of PFC (33% or more) following incubation with anti-FVMA plus C. A similar degree of inhibition was found with hemolytic (anti-sRBC) PFC from FV-infected mice. In contrast, primary vibriolytic PFC from FV-infected mice were not inhibited by anti-FVMA, i.e., they did not carry the virus-induced antigen. These results indicate absolute correlation between viral suppression of a given clone of immunocompetent cells, and antigenic alteration of individual antibody-forming cells due to the virus-infection. Furthermore, the absence of both functional inhibition and virus-induced antigen(s) in the primary immunocompetent cells and the presence of both these virus-related functions in the memory cells (either experimentally sensitized cholera memory cells or naturally sensitized sRBC memory cells) strongly suggested that the latter are selectively susceptible to oncornavirus.