Idiopathic paraproteinaemia V. Expression of Igh1 and Igh5 allotypes within the homogeneous immunoglobulins of ageing (C57BL/LiARij X CBA/BrARij)F1 mouse.
The role of genetic factors linked to the immunoglobulin loci and the development of idiopathic paraproteinaemia (IP)--a benign B-cell proliferative disorder--was investigated in F1 hybrid mice of low (CBA/BrARij) and high (C57BL/LiARij) IP frequency strains. Igh1 and Igh5 allotypes were used as markers for the (parental type) origin of homogeneous immunoglobulins (H-Ig) which appeared in the sera of the F1 mice with ageing. The frequencies of H-Ig in the F1 mice were intermediate with those of the parental strains. The isotype distribution of the H-Ig was 27%, 24%, 12%, 12%, 11%, 10%, 3% and 1% for IgG2a, IgM, IgG1, IgG3, IgG2b, IgD, IgA and IgE, respectively. H-Ig of the IgG2 subclass carried the Igh1b (C57BL) allotype in 98% and the Igh1a (CBA) allotype in 2% cases. Of the IgD H-Ig, 70% carried the Igh5b and 30% the Igh5a determinant. The Igh1 allotype distribution in the bone marrow and spleen plasma cells showed a large variation in the Igh1a/Igh1b ratio among old individual mice and often also between bone marrow and spleen within a single animal with or without a H-Ig component. The categorization of the paraproteinaemias on the basis of their origin showed that 10% of the H-Ig were the result of a transient monoclonal B-cell proliferation; multiple myeloma or lymphoma was found to be responsible for about 1% of the paraproteinaemias; H-Ig fulfilling the criteria for IP were detected in about 42% of cases. The origin of the remaining old age paraproteinaemias could not be determined. These data indicate that the F1 mice develop monoclonal proliferative disorders in a manner more similar to the C57BL than to the CBA parental strain. The allotype associated genetic material from the parental C57BL strain was shown to be mainly responsible for the development of IP in ageing F1 mice.
D000375:Aging; D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D005779:Immunodiffusion; D007126:Immunoglobulin Allotypes / Q000032:analysis*; D007072:Immunoglobulin D / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010265:Paraproteinemias / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D013154:Spleen / Q000637:transplantation
D007126:Immunoglobulin Allotypes; D007072:Immunoglobulin D; D007074:Immunoglobulin G