ABSTRACT
Young Alicia rabbits use VHa-negative genes, VHx and VHy, in most VDJ genes, and their serum Ig is VHa negative. However, as Alicia rabbits age, VHa2 allotype Ig is produced at high levels. We investigated which VH gene segments are used in the VDJ genes of a2 Ig-secreting hybridomas and of a2 Ig+ B cells from adult Alicia rabbits. We found that 21 of the 25 VDJ genes used the a2-encoding genes, VH4 or VH7; the other four VDJ genes used four unknown VH gene segments. Because VH4 and VH7 are rarely found in VDJ genes of normal or young Alicia rabbits, we investigated the timing of rearrangement of these genes in Alicia rabbits. During fetal development, VH4 was used in 60-80% of nonproductively rearranged VDJ genes, and VHx and VHy together were used in 10-26%. These data indicate that during B lymphopoiesis VH4 is preferentially rearranged. However, the percentage of productive VHx- and VHy-utilizing VDJ genes increased from 38% at day 21 of gestation to 89% at birth (gestation day 31), whereas the percentage of VH4-utilizing VDJ genes remained at 15%. These data suggest that during fetal development, either VH4-utilizing B-lineage cells are selectively eliminated, or B cells with VHx- and VHy-utilizing VDJ genes are selectively expanded, or both. The accumulation of peripheral VH4-utilizing a2 B cells with age indicates that these B cells might be selectively expanded in the periphery. We discuss the possible selection mechanisms that regulate VH gene segment usage in rabbit B cells during lymphopoiesis and in the periphery.
Subject(s)
Aging/genetics , Aging/immunology , B-Lymphocytes/immunology , Gene Rearrangement, B-Lymphocyte, Heavy Chain/genetics , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , Mutation , Amino Acid Sequence , Amino Acids/genetics , Amino Acids/isolation & purification , Animals , Animals, Newborn/genetics , Animals, Newborn/immunology , B-Lymphocytes/metabolism , B-Lymphocytes/physiology , Base Sequence , Cell Line , Embryonic and Fetal Development/genetics , Embryonic and Fetal Development/immunology , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/isolation & purification , Genes, Immunoglobulin , Immunoglobulin Allotypes/biosynthesis , Immunoglobulin Allotypes/genetics , Immunoglobulin Allotypes/isolation & purification , Immunoglobulin Heavy Chains/biosynthesis , Immunoglobulin Heavy Chains/isolation & purification , Immunoglobulin Variable Region/biosynthesis , Immunoglobulin Variable Region/isolation & purification , Mice , Molecular Sequence Data , Multigene Family/immunology , RabbitsABSTRACT
The study of immunogenicity of cell-bound haemagglutinin (CHA) of Vibrio cholerae E1 Tor in mice revealed that the CHA was a good antigen when it was adsorbed onto the surface of sheep red blood cells and given orally to mice. The antigen not only induced high levels of various class antibodies which sustained in the intestinal tracts for a long period of time (longer than 6 months) but also the antibodies were protective against homologous cholera challenge. The degree of protection seems to correlate with the level of IgA in the intestinal washing. The protective ability was conferred mainly by anti-CHA.