Mouse homolog of Saccharomyces cerevisiae Spo11 is induced in normal mu(+)B-cells by stimuli that cause germline C-H transcription and subsequent class switch recombination

The first step of Ig heavy chain class switch recombination (CSR) is consid ered to be DNA double strand break (DSB) formation in the two switch (S) re gions (S, and downstream SH), although the underlying mechanism is unknown. Recently, it has been demonstrated that at least Spell, a homolog of the n ovel type II topoisomerase (topo VI) that catalyzes DSB formation, is invol ved in the initiation of meiotic recombination of Saccaromyces cerevisiae. In the present study, we examined whether the mouse homolog of Spo11 is ind uced in normal mouse mu(+)B-cells by stimuli that cause an early step of CS R, germline CH transcription, and subsequent CSR. Two CSR systems were used : IgA CSR induced by all-trans retinoic acid, IL-5, and LPS, and IgG1 CSR i nduced by IL-4 and LPS. Germline transcript and mouse Spo11 expression were analyzed by RT-PCR. In both systems, first germline transcripts were clear ly detected on day 2 and then Spo11 was detected on day 3, increasing there after with time. The time course of changes in Spo11 expression coincided w ith that of CSR. Spo11 seems to be induced by CSR-inducing stimuli, regardl ess of the direction of CSR. These results suggested that mouse Spo11 might participate in the initiation step of CSR. (C) 2000 Academic Press.