B lymphocyte selection and age-related changes in V-H gene usage in mutantalicia rabbits

Young Alicia rabbits use V(H)a-negative genes, V(H)x and V(H)y, in most VDJ genes, and their serum Ig is V(H)a negative. However, as Alicia rabbits ag e, V(H)a2 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 o f a2 Ig(+) B cells from adult Alicia rabbits. We found that 21 of the 25 VD J genes used the a2-encoding genes, V(H)4 or V(H)7; the other four VDJ gene s used four unknown V-H gene segments. Because V(H)4 and V(H)7 are rarely f ound in VDJ genes of normal or young Alicia rabbits, we investigated the ti ming of rearrangement of these genes in Alicia rabbits. During fetal develo pment, V(H)4 was used in 60-80% of nonproductively rearranged VDJ genes, an d V(H)x and V(H)y together were used in 10-26%, These data indicate that du ring B lymphopoiesis V(H)4 is preferentially rearranged. However, the perce ntage of productive V(H)x- and V(H)y-utilizing VDJ genes increased from 38% at day 21 of gestation to 89% at birth (gestation day 31), whereas the per centage of V(H)4-utilizing VDJ genes remained at 15%, These data suggest th at during fetal development, either V(H)4-utilizing B-lineage cells are sel ectively eliminated, or B cells with V(H)x- and V(H)y-utilizing VDJ genes a re selectively expanded, or both. The accumulation of peripheral V(H)4-util izing a2 B cells with age indicates that these B cells might be selectively expanded in the periphery. We discuss the possible selection mechanisms th at regulate V-H gene segment usage in rabbit B cells during lymphopoiesis a nd in the periphery.