Influence of surrogate L chain on DHJH-reading frame 2 suppression in mouse precursor B cells

Haasner, Dirk ; Rolink, Antonius ; Melchers, Fritz

In: International Immunology, 1994, vol. 6, no. 1, p. 21-30

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    Summary
    DHJH rearrangements start in progenitor and precursor B cells and occur in three reading frames (rf). A strong bias for rf I has been noticed in murlne and chicken antibodies, while the representation of rf II has been found suppressed both in peripheral as well as in precursor B cells. H chain gene loci DHJH rearranged in rf II are potentially capable of expressing a truncated DnJHC, protein on the cell surface. Mice incapable of expressing this protein on the surface have previously been shown to have all reading frames represented in near equal frequency, suggesting that membrane-bound DHJHCμ protein 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 gestation, but becomes established when such precursor cell populations are expanded in vitro on stromal cells in the presence of IL-7. H chain gene loci using the DQ52 segment for rearrangements (which contains a stop codon in rf II, thus being unable to make DHJHCμ protein) do not show rf II suppression under these conditions. The same type of fetal liver-derived pro B-l cells from λ5 deficient mice also do not show rf II suppression after in vitro expansion. Bone marrow-derived pre B-I cells from normal mice assayed ex vivo and expanded in vivo show rf II suppression, while the corresponding pre-B I cells from λ5T mice do not. Collectively these experiments suggest that surrogate L chain Is involved in rf II suppression. This may happen by inhibition of proliferation of pre-B cells expressing a complex of DHJHCμ protein and surrogate L chain