Lec 40: Development of B cells Flashcards

1
Q

Outline the development of B lymphocytes, from bone marrow to secondary lymphoid tissues and back again.

A

3 Phases of B-cell development

  • Phase 1: Antigen receptor expression Occurs in bone marrow Process creates genetically diverse cells, 1016 variations Allelic exclusion
  • Phase 2: Elimination of self-reactive cells Occurs in bone marrow
  • Phase 3: Terminal antigen-stimulated differentiation Occurs in secondary lymphoid tissues
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2
Q

Explain how mechanisms of immunoglobulin gene expression in the bone marrow contribute to antibody diversity:

A

Combinatorial diversity through somatic recombination

  • Rearrangement of gene segments to form a functional gene
  • Variable region of both light and heavy chains are rearranged

Junctional diversity: DNA cleavage and repair in the immunoglobulin chain loci

  • RAG creates hairpin and cleaves
    • P (palindromic) nucleotides added
  • Terminal deoxynucleotidyl transferase (TdT) randomly adds nucleotides
    • N (non-templated) nucleotides added
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3
Q

Describe how each B cell produces immunoglobulin of a single antigen specificity.

A
  • Heavy chain is made (VDJ rearrangement) and must bind to surrogate light chain (stand-in for light chain which hasn’t been rearranged yet)
  • Cell either undergoes apoptosis or moves on to rearrangement of light chain gene
  • Light chain must bind to heavy chain or cell undergoes apoptosis
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4
Q

Indicate the mechanisms by which auto-reactive B cells are prevented from causing autoimmune disease.

A

Self-reactive B-cells outside the bone marrow either die by apoptosis or are rendered anergic when they encounter their self-antigen. This is called peripheral tolerance.

figure shows central tolerance because it is developed in a primary lymphoid organ.

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5
Q

Where does central tolerance occur?

A

Primary lymphoid organ

(B cells = bone marrow)

(T cells = thymus)

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6
Q

Define central tolerance (as related to B cells)

A

Mechanisms which ensure B cells leaving the bone marrow are tolerant to all self antigens present in the bone marrow, many of which are present in other tissues.

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7
Q

Define peripheral tolerance (related to B cells)

A

Tolerance induced to antigens outside the bone marrow

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8
Q

What is somatic recombination?

A

DNA recombination that occurs between gene segments. It generates a complete exon composed of VJ(D) segment encoding the variable region of the gene

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9
Q

What is junctional diversity?

A

Diversity created during the process of gene rearrangement by addition or removal of nucleotides at the junctions between gene segments

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