Natural HLA antibodies

Abstract

“Natural antibodies” directed against antigens of the Major Histocompatibility Complex have been observed in aged mice but very seldom in humans. It is likely that HLA natural antibodies are more common than previously supposed: our results suggest they may be found in 1% of normal blood donors. Most of these antibodies seem to be weak and can only be detected when B lymphocytes (BL) are used as target cells in the lymphocytotoxicity technique or when indirect immunofluorescence is used with peripheral blood lymphocytes (PBL). The behavior of these natural IgM antibodies was compared to that of weak immune IgG HLA antibodies detected in the same way. Absorption tests showed that “natural antibodies” were very specifically absorbed, whereas “immune antibodies” could also be absorbed by cells not carrying the specific antigen. Furthermore, about half of the “natural antibodies” detected to date carried the HLA‐B8 specificity. Various hypotheses have been put forward to attempt to explain the appearance of these antibodies.

Antibodies to HLA-E in Nonalloimmunized Males: Pattern of HLA-Ia Reactivity of Anti–HLA-E–Positive Sera

“…The prevalence of IgM that recognizes allo-HLA-Ia in the healthy sera without prior alloimmunization was documented previously (7). The present investigation further confirms the presence of IgM and IgG in healthy male sera reactive to HLA-Ia alleles coated onto different lots of SABs.…”

“…The progress made so far on the discovery of natural HLA Abs in humans projects that, in the future, a greater number and incidence of natural allo-HLA IgG Abs will be recorded in healthy nonalloimmunized males. A number of investigators provided different explanations for the presence of natural HLA Abs (7,11,12,43). Some contended that they are the result of a polyclonal, continuous immune response against exogenous Ags (5, 6, 8-12).…”

“…Some contended that they are the result of a polyclonal, continuous immune response against exogenous Ags (5, 6, 8-12). Tongio et al (7) thought that natural HLA-Ia reactivity of sera could be due to spontaneous secretion of Abs by one or more B cell clones developed against common autoantigens (7). The number of HLA-Ia specificities of natural Abs in Mexican healthy nonalloimmunized males, as assessed in neat sera or sera diluted 1:3, range from 1 to 64, with MFI cutoff at 500.…”

“…Tongio et al (7) suggested that natural allo-HLA Abs could be the result of spontaneous secretion of a B cell clone directed against a common autoantigen. Whether any self-Ags that mimic HLA-Ia alleles could elicit Abs that react to HLA-Ia alleles has never been considered, primarily due to Burnet's hypothesis of clonal selection (24,25), which forbids immunity against selfAgs.…”

Therapeutic preparations of IVIg contain naturally occurring anti–HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles

“…Consequently, it may contain HLA antibodies because several allo-HLA antibodies are known to occur naturally in the sera of both men (nonalloimmunized) and women. [9][10][11][12][13] MoralesBuenrostro et al 11 demonstrated the specificities and incidence of these allo-HLA-I Abs in nonalloimmunized males. Neither the origin nor cause of anti-HLA Abs occurring in healthy individuals has been established.…”