Use of the most J[sub H]-proximal human Ig H chain V region gene, V[sub H6], in the expressed immune repertoire

Journal Article · Tue Jun 01 04:00:00 EDT 1993 · Journal of Immunology; (United States)

OSTI ID:6180400

Varade, W S; Marin, E; Kittelberger, A M; Insel, R A ^[1]

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1. Univ. of Rochester School of Medicine and Dentistry, NY (United States)

V[sub H6], the most 3[prime] human H chain V region gene, is preferentially expressed in the preimmune repertoire of the developing human fetus. To determine whether V[sub H6] contributes to the immune repertoire, the authors amplified and sequenced from human spleen RNA V[sub H6] rearrangements that were isotype-switched to IgG. Eighteen distinct in-frame V[sub H6] clones were sequenced. Definitive assignment to C[gamma]1 could be made in the majority of clones, and all had undergone extensive somatic hypermutation in the V region with an average of 14 (range, 2 to 25) mutations/281 bp in the V[sub H6] segment. The overall frequency of somatic mutation was 5.2% of the total nucleotides sequenced. Replacement somatic mutations were targeted to the complementarity determining region, and the complementarity determining region had higher replacement to silent mutation ratios, consistent with antigenic selection. Silent somatic mutations were also significantly more frequent in the complementarity determining region compared to the framework region. Five clones were derived from the same V[sub H6]D[sub xp[prime]1]J[sub H6] rearrangement, each containing unique and shared mutations. All D[sub H] segments used by independently arising clones were unique, and all D[sub H] reading frames were seen. N segments were lacking at either the 5[prime]K[sub H[minus]]J[sub H] junction or the 3[prime]D[sub H[minus]]J[sub H] junction in 7 of 13 independent rearrangements. D[sub H[minus]]D[sub H] recombinations were frequently observed, and there was biased usage of J[sub H3b] and J[sub H4b] in the clones. The data imply that a high degree of diversity arises from use of this 3[prime]-V[sub H] gene in the immune repertorie. 70 refs., 3 figs., 1 tab.

• OSTI ID: 6180400
• Journal Information: Journal of Immunology; (United States), Journal Name: Journal of Immunology; (United States) Vol. 150:11; ISSN 0022-1767; ISSN JOIMA3
• Country of Publication: United States
• Language: English

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