DEVELOPMENTAL SPECIFICITY OF IMMUNOGLOBULIN HEAVY-CHAIN SWITCH REGIONRECOMBINATION ACTIVITIES

To understand the regulation of enzymes that carry out immunoglobulin heavy chain class switch recombination, we have assayed recombination of extrachromosomal substrates carrying switch region sequences in cel l lines representing different stages of lymphoid cell development. Bo th pre-B and mature B cell lines supported switch substrate recombinat ion, but B cell lines derived from later stages of cell development di d not. Recombination did not occur in an erythroid or a macrophage lin e. Most recombination junctions in the substrates recovered from trans fection of pre-B and B cells mapped to heterogeneous sites within the S mu and S gamma regions, as do chromosomal switch junctions. Some rec ombination did occur in T cell lines, but most recombination junctions involved an upstream promoter and did not map preferentially to S reg ions. Culture of the pre-B cell lines PD31 and 70Z/3 with LPS increase d recombination two-fold, to levels approaching those observed in LPS- cultured primary B cells. These results show that the full complement of factors necessary for switch recombination is present only in cells representing a limited spectrum of B cell development and that LPS, w hich can activate resting splenic B cells to carry out chromosomal rec ombination, can also stimulate recombination activity in immortalized pre-B cell lines. (C) 1997 Elsevier Science Ltd.