Enhancement activity of anti-mycobacterial sera in experimental Mycobacterium bovis (BCG) infection in mice

Abstract

The passive transfer of rabbit anti-mycobacterial immunoglobulins was directed against either living or soluble extracts of Mycobacterium tuberculosis strain H37Rv, which promotes the multiplication of the BCG strain of M. tuberculosis in the spleen of mice infected with low doses of this latter strain. This enhancing effect was reduced significantly when antisera were absorbed with living BCG. Moreover, such treatment led to the removal of all hemagglutinating antibodies when antisera were tested against either BCG or H37Rv soluble extracts. Therefore, it is most probable that the enhancing effect is related to the presence of mycobacterial antibodies.

Serum Therapy for Tuberculosis Revisited: Reappraisal of the Role of Antibody-Mediated Immunity againstMycobacterium tuberculosis

“…Some investigators who did not demonstrate antibody-mediated protection nevertheless pointed out that antibodies important for protection may have been missing from their preparations (90,92). A disease-enhancing effect of antibodies was found by one investigator (42). The studies with B-cell-deficient mice (118) and those with high and low antibody responsiveness (45) produced results consistent with a role for antibody-mediated immunity in protection against TB.…”

“…(b) Forget et al In 1976, Forget et al reported that administration of rabbit immune sera via i.p. injection enhanced infection by promoting the multiplication of BCG in the spleens of mice (42). Immune sera were produced in rabbits by repeated i.v.…”

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

“…Moreover, some monoclonal Mtb IgG1 can enhance bacterial replication in vitro, demonstrating the potential to exacerbate disease (27). Finally, polyclonal serum from Mtb infected rabbits can enhance BCG infection in mice (123). Thus, specific subclasses such as IgG1 and IgG3 in the context of monoclonality or polyclonality may participate in the induction of pro-inflammatory downstream consequences as seen in active TB disease and potentially favor the bacteria.…”

Increase of tuberculous infection in the organs of B cell-deficient mice

“…These results have led to the conclusion that antibodies and, by inference, B cells, play no obvious beneficial role in immunity to tuberculosis. Despite this prevailing opinion, the following experimental and clinical data indicated, at least indirectly, a possible regulatory function of B cells: (i) Igh genes influence the magnitude of M. bovis bacille Calmette-Guérin (BCG) granuloma formation [4,5]; (ii) passive transfer of antibodies promoted the multiplication of BCG in infected mice [6]; (iii) in tuberculosis patients, serum antibody levels against the 38-kD antigen of M. tuberculosis associated with severe forms of tuberculosis, whilst those against the 16-kD antigen associated with milder disease [7]. Furthermore, the beneficial role of antibodies to lipoarabinomannan (LAM) was proposed on the grounds that localized disease in children associated with higher antibody levels than those in disseminated disease [8].…”