Bursa of Fabricius

Kalle‐Pekka Nera, University of Turku, Turku, Finland
Minna K Kyläniemi, University of Turku, Turku, Finland
Olli Lassila, University of Turku, Turku, Finland

Published online: November 2015

DOI: 10.1002/9780470015902.a0000506.pub4

Abstract

The bursa of Fabricius plays a central role in the development of the antibody‐producing B‐lymphocyte lineage in birds. It consists of more than 10 000 follicles surrounded by connective tissue. These follicles provide an appropriate microenvironment for generating a primary repertoire of antibodies. Immunoglobulin gene diversification is achieved by gene conversion and is antigen independent. Bursal B cells undergo very rapid cell division while expressing AID, UNG, Pax5 and Bcl6, genes that are also expressed in proliferating germinal center B cells. By the time of sexual maturity, the bursa involutes and the only source of B‐cell renewal in adult birds is the pool of postbursal B cells in the peripheral lymphoid organs. Bursal B‐cell line DT40 provides a unique model system for gene‐targeting studies clarifying the B‐cell development, function and Ig diversification.

Key Concepts

  • Bursa of Fabricius is the primary site for B‐cell development.
  • Bursa is the site of primary antibody repertoire formation in birds.
  • Bursa involutes at the time of sexual maturity.
  • Antibody diversification in the bursa of Fabricius is antigen independent and occurs mostly by Ig gene conversion.
  • Bursal‐derived DT40 B‐cell line provides a reverse genetic model to study molecular function of B cells.

Keywords: aves; B cells; Ig diversification; gene conversion; haematopoiesis; DT40; evolution

Figure 1. Anatomy and structure of the avian bursa of Fabricius. (a) Anatomical location of the chicken thymus and the bursa of Fabricius, and a cross‐section of the bursa of Fabricius. The bursa has a highly folded surface surrounding the central lumen, which is connected to the intestine by the bursal duct. The lymphoid follicles are situated within the longitudinal plicae. Altogether, the bursa contains approximately 10 000 follicles. Between the bursal medulla and lumen is the follicular‐associated epithelium (FAE). (b) Avian B‐cell development. The progenitor cells seeding the bursal primordium originate from the paraaortic mesenchyme. These prebursal ‘stem cells’ (prebursal B‐cell progenitors) are committed to the B‐cell lineage before bursal colonisation. Within the bursal follicles the surface immunoglobulin‐expressing bursal progenitors start to divide and diversify their immunoglobulin V genes. The proliferating bursal B cells are densely packed in the cortical part of the bursal follicles. The medulla (M) contains mainly loosely packed lymphocytes and stromal cells. Starting shortly before hatching, diversified B cells start to emigrate from the bursa; however, more than 95% of bursal B cells die by apoptosis. Within the peripheral lymphoid organs, postbursal B cells can further modify their immunoglobulin gene specificity by gene conversion and by somatic hypermutation. The peripheral lymphoid organs cannot, however, replace the important function of the bursa as a mutant‐generating organ.
Figure 2. Comparison of human and avian immunoglobulin (Ig) gene diversification. While humans have multiple functional Ig variable (V) regions, avians have only one. Thus, no considerable variation is generated by gene rearrangement in avians. Ig V region diversity is generated by gene conversion, which uses upstream V pseudogene segments as templates for homologous recombination generating mutations to the recombined functional V region. Further diversification is achieved by somatic hypermutation (SHM).
Figure 3. Schematic comparison of human and avian B‐cell development. In human (and mouse) B cells develop in the foetal liver and bone marrow. During pro‐B‐cell stage, Ig heavy chains (IgH) are rearranged and expressed on the cell surface with surrogate light chains as part of a pre‐BCR complex. Following Ig light (IgL), chain rearrangement leads to the expression of completed IgM on the cell surface of immature B cells. Owing to the multiple Ig V(D)J regions, multitude IgMs with variable specificity are generated. In contrast, birds recombine IgH and IgL chains simultaneously during the prebursal development, and no considerable variation in Ig specificity is generated. The Ig diversity is primarily achieved by gene conversion and to lesser extent by somatic hypermutation (SHM) at the bursal stage of the development. SHM further adds variability to Ig specificity at the stage of germinal centre (GC) B cells in both human and birds, but in avian GCs also Ig gene conversion occurs at early stages of GC development.
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Related Sub-Topics:

Tissues of the Immune System | Antibodies | Genes, Molecules and Cellular Processes | Acquired (Adaptive) Immunity | Cell Differentiation and Stem Cells | Cells of the Immune System | Developmental Models
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Article Title: Bursa of Fabricius
 
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Nera, Kalle‐Pekka, Kyläniemi, Minna K, and Lassila, Olli(Nov 2015) Bursa of Fabricius. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000506.pub4]