Kinetics of escape from suppression of Ig heavy chain allotypes in multiheterozygous rabbits

Abstract

Three rabbits of genotype a1n81f73g74/a2n82f71g75 which had been injected at birth with anti-a l (VH) antiserum and which were previously shown to be suppressed for the paternal allotypes a 1, n81, f73 and g74 at 8 weeks of age, were monitored over a 2-year period for the concentration of suppressed and nonsuppressed allotypes in their sera. In all three suppressed animals, the f73 (C alpha) and g 74 (C alpha) allotypes were expressed again at a much greater rate than the a1 (VH) and n81 (C mu) allotypes. In one suppressed animal, the a l (VH) allotype was re-expressed at a much greater rate than the n81 (C mu) allotype and reflected primarily the reappearance of a l IgG. Thus, the escape from allotype suppression in this animal was in the order IgA, IgG, IgM which is the reverse of the order of appearance of these Ig classes during ontogeny. While the al(VH) and n81 (C mu) allotyes remained suppressed, the f73 (C alpha) and g74 (C alpha) allotypes were re-expressed to the same concentration as in the unsuppressed controls, and no compensatory decrease of the f71 and g75 allotypes occurred. During the re-expression of the f73 and g74 allotypes, the ratio of the concentrations of f73/g74 remained approximately constant.

B Lymphocyte Development in Rabbit: Progenitor B Cells and Waning of B Lymphopoiesis

“…These undiversified VDJ genes could be derived from newly formed B cells or B cells that have self renewed since early in ontogeny. However, we think that lymphopoiesis in adults contributes little, if any, to the repertoire because of allotype suppression experiments in which neonatal or in utero treatment of rabbits heterozygous for C or V H allotypes with Abs against one of the allelic allotypes resulted in life-long suppression of IgM of that allotype (44,45). These data demonstrate that B cells expressing the suppressed IgM allotype do not reemerge over time despite trace levels of B lymphopoiesis in adult rabbits.…”

Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis

“…In addition to changes in hematopoietic progenitors, changes to the BM microenvironment also contribute to impaired B cell development in aged individuals (5, 12–15). In rabbits, allotype suppression experiments (16), as well as the nearly complete loss of B lineage progenitors and B cell recombination excision circles (BRECs) in the BM suggested that B lymphopoiesis arrests by 2–4 months of age (17). The transfer of hematopoietic progenitors from adult rabbits into young irradiated recipients showed that the decline in B lymphopoiesis is likely due primarily to changes in the BM microenvironment rather than to hematopoietic progenitors (18).…”

Somatic diversification of IgH genes in rabbit

“…As a result, these rahbits did not express serum Ig of the paternal allotype, and in other experiments with allotype suppressed rabbits, very few precursor cells expressing the suppressed allotype were found (22). The Vna-allotype suppression was shown to continue for at least 2 years (23). Similar allotype suppression experiments in mice heterozygous for IgH allotypes also resulted in suppression of Ig and of B lymphocytes that express the allotype against which the antihody was directed.…”