Physical Mapping of the Bovine Immunoglobulin Heavy Chain Constant Region Gene Locus

Bovine antibodies have recently attracted increasing attention, as they have been shown to exhibit prophylactic and therapeutic properties in selected infectious diseases in humans. In the present study, we have isolated bacterial artificial chromosomes and cosmid clones containing the bovine JH, μ, δ, γ1, γ2, γ3, ϵ, and α genes, which allowed us to make a contig of the genes within the bovine IGHC locus. The genes are arranged in a 5′-JH–7 kb–μ–5 kb–δ–33 kb–γ3–20 kb–γ1–34 kb–γ2–20 kb–ϵ– 13 kb–α-3′ order, spanning ∼150 kb DNA. Examination of the bovine germline JH locus revealed six JH segments, two of which, JH1 and JH2, were shown to be functional although there was a strong preference for expression of the former. Sequence alignment of the bovine 5′ Eμ enhancer core region with those of other mammals, demonstrated an absence of the μE3 motif and a shortened spacer between the μA and μB sites within the bovine Eμ enhancer core region. Furthermore, the essential sequence element for class switching, switch μ, spanning ∼3-kb repetitive sequence and abundant in the switch region motifs CTGGG (187 repeats) and CTGAG (127 repeats), was identified immediately upstream of the μ gene. A further sequence comparison revealed that the bovine IGHC genes display an extensive polymorphism leading to expression of multiple antibody allotypes.