INFLUENCE OF SURROGATE-L CHAIN ON D(H)J(H)- READING FRAME-2 SUPPRESSION IN MOUSE PRECURSOR B-CELLS

D(H)J(H) rearrangements start in progenitor and precursor B cells and occur in three reading frames (rf). A strong bias for rf I has been no ticed in murine and chicken antibodies, while the representation of rf Il has been found suppressed both in peripheral as well as in precurs or B cells. H chain gene loci D(H)J(H) rearranged in rf II are potenti ally capable of expressing a truncated D(H)J(H)C(mu) protein on the ce ll surface. Mice incapable of expressing this protein on the surface h ave previously been shown to have all reading frames represented in ne ar equal frequency, suggesting that membrane-bound D(H)J(H)C(mu) prote in is involved in the suppression of rf II. In this paper we show that suppression of rf II is not yet established in c-kit(+) CD43(+) IL-7/ stromal cell-reactive pre-B I cells of fetal liver at day 15 of gestat ion, but becomes established when such precursor cell populations are expanded in vitro on stromal cells in the presence of IL-7. H chain ge ne loci using the D-Q52 segment for rearrangements (which contains a s top codon in rf II, thus being unable to make D(H)J(H)C(mu) protein) d o not show rf II suppression under these conditions. The same type of fetal liver-derived pre B-l cells from lambda 5 deficient mice also do not show rf II suppression after in vitro expansion. Bone marrow-deri ved pre B-I cells from normal mice assayed ex vivo and expanded in viv o show rf II suppression, while the corresponding pre-B I cells from l ambda 5T mice do not. Collectively these experiments suggest that surr ogate L chain is involved in rf II suppression. This may happen by inh ibition of proliferation of pre-B cells expressing a complex of D(H)J( H)C(mu) protein and surrogate L chain.