Polyclonal B Cell Activation of IgG2a and IgG2b Production by Infection of Mice with Lactate Dehydrogenase-Elevating Virus Is Partly Dependent on CD4⁺Lymphocytes

Abstract

Concentrations of IgM and IgG isotypes were determined by capture ELISA in plasma of Swiss, BALB/c and C58/M mice. Plasma IgG isotype concentrations, especially of IgM, IgG1 and IgG2a, varied considerably between mouse strains, batches of mice of the same strain and individual mice and as a function of age. Infection of the mice with LDV, which is known to replicate primarily in a subpopulation of macrophages, consistently resulted in a rapid elevation of plasma IgG2a (or of IgG2b in some Swiss nu/+ mice), but no plasma IgG increases were observed in mice immunized with inactivated LDV. Plasma IgG2a elevation after LDV infection was greatly delayed and reduced by depletion of the mice of CD4+, but not of CD8+, T cells by administration of protein-G-purified anti-CD4 or anti-CD8 mAbs, and completely inhibited by repeated treatment of the mice with cyclophosphamide. Treatment with anti-CD4 mAbs, or cyclophosphamide also greatly reduced the production of anti-LDV antibodies, while not significantly affecting the replication of LDV in these mice. Nude Swiss mice also failed to produce anti-LDV antibodies, though supporting normal LDV replication. Plasma IgM, IgG1, IgG2a and IgG2b levels increased in LDV-infected nu/nu mice, but similar changes were observed in uninfected mice. The results indicate that the LDV-induced polyclonal activation of B cells requires productive LDV infection of mice and is, at least partly, dependent on functioning CD4+ cells. They suggest that productive infection of the LDV-permissive subpopulation of macrophages leads to the activation of CD4+ T lymphocytes of subset 1 and their Spleen cells from 5-day LDV-infected BALB/c mice incorporated [3H]thymidine 2-3 times more rapidly in vitro than spleen cells from companion uninfected mice, whereas their responses to concanavalin A and lipopolysaccharide were reduced 60-70%.

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

“…The appearance of inefficient neutralizing Abs is delayed, appearing 1-2 mo after infection (38). LDV produces polyclonal B cell activation (39,40) that results in the formation of immune complexes and autoantibodies (41,42). These have been reported not to contain anti-LDV Abs but appear to be complexes of autoantibodies and self-antigens (43) and hydrophobic aggregates that spontaneously adsorb to polystyrene (44).…”

Neonatal Infection of Mice With Lactate Dehydrogenase-elevating Virus Results in Suppression of Humoral Antiviral Immune Response but does not Alter the Course of Viraemia or the Polyclonal Activation of B Cells and Immune Complex Formation

“…The polyclonal activation of B cells during LDV infection of adult mice results in significant permanent increases in IgG, predominantly IgG2a and/or IgG2b, up to 5 to 10 mg/ml (Li et al, 1990;Coutelier et al, 1988Coutelier et al, , 1990. The results in Fig.…”

“…Total immunoglobulins of different isotypes were measured using an ELISA method described previously (Li et al, 1990). ELISA plates (Nunc Immunoplate MaxiSorp F90; Gibco) were coated with goat anti-mouse IgG (Sigma).…”

“…Other indicators of polyclonal activation of B cells in adult mice after LDV infection are increases in B cell proliferation and production of IgG2a and IgG2b in splenocyte cultures (Coutelier et al, 1990;Li et al, 1990). Both of these changes begin to become detectable within a week p.i.…”

Papel das células TCD4⁺FoxP3⁺ (T_reguladoras) na fase aguda da infecção murina pelo <i>Trypanosoma cruzi</i>.

“…No entanto, nos primeiros dias da infecção murina pelo T. cruzi, semelhante ao que ocorre em infecções por muitos outros microorganismos, tais como protozoários (Greenwood, 1974); (Rosenberg, 1978), vírus (Coutelier et al, 1990); (Li et al, 1990;Hunziker et al, 2003), bactérias (Sultzer, 1978) e mesmo helmintos (Lopes et al, 1990), ocorre uma intensa proliferação no baço de células B e T (Ortiz-Ortiz et al, 1980) ocorrendo a produção de anticorpos com diferentes especificidades. Esta é uma reação imune inesperada, na medida em que os linfócitos expandidos e os anticorpos secretados exibem especificidades não relacionadas ao parasita (Minoprio et al, 1988).…”