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The events of B-cell differentiation can be reconstructed in part through an analysis of the organisation of heavy-chain gene segments in differentiated B cells. A mouse immunoglobulin alpha heavy-chain gene is composed of at least three noncontiguous germ-line DNA segments--a VH gene segment, a JH gene segment associated with the Cmu gene segment, and the C alpha gene segment. These gene segments are joined together by two distinct types of DNA rearrangements--a V-J joining and a CH switch.

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(V and C) and the a heavy chain has four (V, CHi, CH2, and CH3) (2). The variable and constant regions of light chains are encoded by three distinct gene segments, V (approximately residues 1-99), J or joining (approximately residues 100-112), and C (approximately residues 113-219) (3, 4). The V and J segments encode the classical V region. Each of these DNA segments is separated by intervening nucleotide sequences in embryo or undifferentiated DNA (4). Studies of myeloma DNA suggest that these gene segments are rearranged during the differentiation of antibody-producing cells. However, in myeloma DNA, intervening sequences still separate the V and C segments (4). These intervening sequences must be removed from nuclear RNA transcripts of light chain genes by RNA splicing (5). Thus, DNA rearrangements and RNA splicing appear to be important events in the differentiation of antibody-producing cells (6).We are interested in analyzing the genes coding for heavy chains in embryo and myeloma DNA to determine whether sequence rearrangements occur during differentiation that are comparable to those seen for light chain gene segments (4). Our initial approach has been to isolate genomic clones from a library of recombinant Charon 4A bacteriophage containing long fragments of M603 myeloma DNA. In this paper we report the characterization of one clone containing both VH and Ca regions. DP50SupF (19,21). Duplicate nitrocellulose filters from each plate were prehybridized in 1 M NaCl/0.045 M trisodium citrate/0.2% bovine serum albumin/0.2% Ficoll/0.2% polyvinylpyrrolidone/0.1% sodium Abbreviations: V, variable; C, constant; NaDodSO4, sodium dodecyl sulfate; kb, kilobase(s); IVS, intervening sequence(s). f To whom reprint requests should be addressed. 857The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.