The appendix functions as a mammalian bursal equivalent in the developing rabbit

In this paper we present genomic DNA sequence and histological evidence that the appendix is a site of diversification of the rabbit's primary antibody repertoire. By 6 weeks after birth, the B cell follicular regions of the rabbit appendix and the distribution of the resident lymphoid cells bear a strong morphological resemblance to similar regions within two primary lymphoid tissues, the chicken bursa and the sheep ileal Peyer's patch. However, similarities between the rabbit appendix, chicken bursa and sheep ileal Peyer's patch end as these animals reach adulthood. The rabbit appendix undergoes morphological and cellular distribution changes as it matures taking on the appearance of a secondary lymphoid tissue, while the sheep ileal Peyer's patch and the chicken bursa both involute. We determined DNA sequences of PCR amplified rearranged variable region genes from germinal center B cells of 6 week old rabbits isolated from several different appendix dark zones and light zones. There was a trend toward a higher degree of diversification from the germ-line VH gene DNA sequence in dark zones than light zones. It is likely that both gene conversion and somatic hypermutation are responsible for the nucleotide changes we observed. Our findings suggest that the rabbit appendix functions as a mammalian bursal equivalent early in development. As the rabbit matures, the appendix appears to evolve into a secondary lymphoid tissue resembling secondary GALT in appearance and possibly in function.