Production of an Antibody Deficiency Syndrome in Rabbits by Neonatal Removal of Organized Intestinal Lymphoid Tissues

Cooper, Andrea M.; Perey, Daniel Y. E.; Gabrielsen, A E; Sutherland, David E.R.; McKneally, Martin F.; Good, Robert A.

doi:10.1159/000229975

Cited by 101 publications

(46 citation statements)

References 30 publications

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“…shown that removal at birth of appendix and other GALT (Sacculus rotundus and Peyer's patches) reduced considerably the B cell response in this species 4 . However at the same time, it was shown that, in the mouse and human models, transfer of bone marrow precursors could restore the B cell lineage of the receiver 5,6 .…”

Section: Discussionmentioning

confidence: 79%

A bird's eye view on human B cells

Weill

Weller

Reynaud

2004

Seminars in Immunology

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Section: Discussionmentioning

confidence: 79%

A bird's eye view on human B cells

Weill

Weller

Reynaud

2004

Seminars in Immunology

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“…After the description of the role of the bursa of Fabricius in the immune function of the chicken many investigators hunted for the mammalian homologue. At first, the rabbit appendix received much attention but there was no clear evidence at that time to show that the appendix played a crucial role in B-cell development [6,20,21]. Later the ileal PP of ruminants was proposed to be a bursal equivalent [55,102].…”

Section: Introductionmentioning

confidence: 99%

The sheep and cattle Peyer’s patch as a site of B-cell development

et al. 2006

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-In sheep and cattle, the ileal Peyer's patch (PP), which extends one-two meters along the terminal small intestine, is a primary lymphoid organ of B-cell development. B-cell diversity in the ileal PP is thought to develop by combinatorial mechanisms, gene conversion and/or point mutation. These species also have jejunal PP that function more like secondary lymphoid tissues concerned with mucosal immune reactions. These two types of PP differ significantly in their histology, ontogeny and the extent of lymphocyte traffic. The prenatal development of follicles in the PP begins first in the jejunum during the middle of gestation and then in the ileum during late gestation. B-cells proliferate rapidly in the ileal PP follicle; up to five percent of these cells survive while the majority dies by apoptosis, perhaps driven by the influence of environmental antigen and/ or self-antigen. The surviving cells migrate from the ileal PP and populate the peripheral B-cell compartment. By adolescence, the ileal PP has involuted but the function of jejunal PP, compatible with a role as secondary lymphoid organ, continues throughout life. In this review, we focus on the development of PP as a site of B-cell repertoire generation, positive and negative B-cell selection, and the differences between ileal PP and jejunal PP.

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“…Weinstein et al (7), for example, determined VDJ gene nucleotide sequences from appendix follicles of 6-wk-old rabbits and found highly diversified, clonally related VDJ genes, which strongly implicates rabbit appendix follicular germinal centers as sites of VDJ gene diversification. In an earlier study, Cooper et al (8) surgically removed GALT from newborn rabbits and found that they had decreased serum Ig levels, fewer circulating lymphocytes, and diminished Ab responsiveness to several Ags. More recently, Vajdy et al (9) examined diversification of the Ab repertoire in GALT-less rabbits, similar to those used in the study by Cooper et al (8), and found that, until 5 mo of age, IgM VDJ genes from peripheral B cells had undergone little diversification compared with those of control rabbits.…”

mentioning

confidence: 99%

Intestinal Microflora and Diversification of the Rabbit Antibody Repertoire

Lanning

Sethupathi

Rhee

et al. 2000

The Journal of Immunology

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The rabbit establishes its primary Ab repertoire by somatically diversifying an initial repertoire that is limited by restricted V H gene segment usage during VDJ gene rearrangement. Somatic diversification occurs in gut-associated lymphoid tissue (GALT), and by about 1-2 mo of age nearly all Ig VDJ genes are somatically diversified. In other species that are known to establish their primary Ab repertoire by somatic diversification, such as chicken, sheep, and cattle, diversification appears to be developmentally regulated: it begins before birth and occurs independent of exogenous factors. Because somatic diversification in rabbit occurs well after birth in GALT, the diversification process may not be developmentally regulated, but may require interaction with exogenous factors derived from the gut. To test this hypothesis, we examined Ab repertoire diversification in rabbits in which the appendix was ligated shortly after birth to prevent microbial colonization and all other organized GALT was surgically removed. We found that by 12 wk of age nearly 90% of the Ig VDJ genes in PBL were undiversified, indicating that intestinal microflora are required for somatically diversifying the Ab repertoire. We also examined repertoire diversification in sterilely derived remote colony rabbits that were hand raised away from contact with conventional rabbits and thereby acquired a different gut microflora. In these remote colony rabbits, GALT was underdeveloped, and 70% of the Ig VDJ genes in PBL were undiversified. We conclude that specific, currently unidentified intestinal microflora are required for Ab repertoire diversification. The Journal of Immunology, 2000, 165: 2012-2019.T he rabbit is one of a few vertebrate species known to make limited use of combinatorial joining of multiple V H, D H , and J H gene segments during Ig heavy chain gene rearrangement. Although there are more than 100 V H gene segments available within the rabbit Ig heavy chain locus, many of which appear to be potentially functional (1), the 3Ј-most V H gene segment, V H 1, is utilized in 80 -90% of VDJ gene rearrangements (2). Most of the remaining 10 -20% of VDJ gene rearrangements utilize only two other V H gene segments, V H x and V H y (3). Rabbit B cells diversify their VDJ genes in gut-associated lymphoid tissue (GALT) 4 at 1-2 mo of age through two targeted mutational processes: a somatic gene conversion-like mechanism that transfers tracts of nucleotide sequence from upstream V H gene segment donors into the rearranged V H gene segment (4), and somatic hypermutation that distributes point mutations throughout the entire VDJ gene (5-7). At that time, the B cell population is also expanded through proliferation in GALT. B cell proliferation and Ig VDJ gene diversification in GALT results in a large population of B cells that express a wide range of Ab specificities.Several studies have established the importance of GALT in B cell proliferation and VDJ gene diversification. Weinstein et al. (7), for example, determined VDJ gene nucleotide...

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Production of an Antibody Deficiency Syndrome in Rabbits by Neonatal Removal of Organized Intestinal Lymphoid Tissues

Cited by 101 publications

References 30 publications

A bird's eye view on human B cells

A bird's eye view on human B cells

The sheep and cattle Peyer’s patch as a site of B-cell development

Intestinal Microflora and Diversification of the Rabbit Antibody Repertoire

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