At least two types of somatic recombination are necessary for the generation of a complete immunoglobulin gamma 2b gene from germ-line DNA sequences. The first type of recombination consists of the assembly of three separate DNA segments, each encoding a different part of the variable region. The second type of recombination replaces the exons coding for the constant region of the mu chain with those coding for the same region of the gamma 2b chain. The DNA sequencing studies suggest that the two types of recombination operate by different mechanisms.

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From endonuclease EcoRI partial libraries of DNAs from mouse embryo and MOPC 141, a -y2b-producing myeloma, clones were isolated by using a DNA fragment carrying the 72b constant (C) region gene as a hybridization probe. One clone from MOPC 141 contained a heavy chain variable (V) gene and the C7y2b gene, as demonstrated by R-loop mapping. The V gene and C gene in this clone were separated by a 3.9-kilobase intron. The characterization of this clone as well as the embryonic clones suggest that at least two recombination events occurred to create the 7Y2b gene in MOPC 141.One of the events is analogous to the V-J joining previously demonstrated in the light chain genes, which brings the major part of the V gene next to a short coding sequence (J). The other event we refer to as "CI-C'y2b switch recombination" because a portion of the intron between the V gene and C gene of the rearranged 72b gene is derived from the 5' flanking sequence of the emb onic C1s gene. A model suggesting how the phenomenon of switch seen in lymphocytes may occur is presented. The notion that DNA segments in mouse embryo are rearranged during the ontogeny of a bone marrow-derived (B) lymphocyte to create a X or K immunoglobulin light chain gene has been demonstrated (1, 2). Essentially, this process involves bringing into proximity a DNA segment coding for one of multiple variable (V) regions with a DNA segment coding for the corresponding constant (C) region. The detailed studies of the sequence organization before and after recombination have revealed that the V region is actually encoded in two separate DNA segments (3, 4). For example, in the XI system the major part of the V region (residues 1-97) is encoded in the V DNA segment, whereas the rest of the V region (residues 98-109) is encoded in a short DNA segment referred to as J DNA. A recombination event between the 3' end, relative to the direction of transcription, of the V DNA segment and the 5' end of the J DNA segment joins these DNA segments in the B lymphocyte.The J DNA segments have been mapped to the 5' side of both CXI and CK genes. Whereas in the XI system a single J DNA segment has been found 1.2 kilobases (kb) away from CXI (3, 5), in the K system there is a cluster of at least five J DNA segments in the range of 2.5 to 4 kb away from the CK gene (6). The possibility that the J DNA segment, in addition to providing a recombination point for any V DNA, may also contribute to the antibody diversity has been suggested and may explain the need for a cluster of J DNA segments (6, 7).Because the heavy chain polypeptide is also composed of a V region and a C region, one might assume that what has been established at the DNA level for light chains will be true for heavy chains. In principle, this is probably so, although the expression of heavy chains has some features that make it considerably more complex than that of light chains. The nature of this complexity is revealed by the existence of at least eight different C regions. Each of these C regions appears to sh...

In Escherichia coli, the structural gene for purine nucleoside phosphorylase, deoD, is subject to insertional inactivation by prophage lambda. From one such secondary site lambda lysogen, strain SP265, one may isolate deletions that remove all or part of the trpR gene and other genes in the deo-thr sector of the E. coli chromosome. Specialized transducing phages harboring serB+ and trpR+ were liberated following induction of SP265. All such phages were N-defective, bio-type pseudolysogens whose DNA persisted in the form of plasmids. A collection of transducing phages, differing in their complement of bacterial DNA, was used to locate cleavage sites for BamHI, SalI, and PvuI within the deoD-trpR region of the E. coli genome. The trpR gene lies within a specific 950 base pair BamHI-PvuI segment. A 1250 base pair BamHI fragment carrying a functional trpR gene was cloned into the amplifiable plasmid pBR322. A single SalI site in this fragment was shown to lie within the TrpR gene. In two situations where increased gene dosage might generate elevated amounts of Trp repressor (N-defective trpR+ pseudolysogens and strains harboring pBR322 trpR+ plasmids) neither tryptophan auxotrophy, enhanced sensitivity to DL-5-methyl-tryptophan, nor super repression of the tryptophan biosynthetic enzymes was observed.

To assess the role of interleukin-1 (IL-1) in cutaneous leishmaniasis, Leishmania major-infected mice were treated with an anti-IL-1 receptor monoclonal antibody, LA-15.6. MoAb LA-15.6 prevents binding of IL-1 to both the T cell and B cell/macrophage forms of the IL-1 receptor. We found that treating with LA 15.6 inhibited the development of cutaneous lesions of L. major in both genetically-susceptible and resistant mice. Interestingly, this treatment had little or no effect on parasite numbers in the lesions or on the cytokines (interferon-gamma, interleukin-4) that the animals produced in response to infection with the parasite. These results suggest that although IL-1 plays a detrimental role in cutaneous leishmaniasis, it does not mediate this effect by altering the parasite-specific T cell response.