Lec 40: Development of B cells Flashcards
Outline the development of B lymphocytes, from bone marrow to secondary lymphoid tissues and back again.
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
Explain how mechanisms of immunoglobulin gene expression in the bone marrow contribute to antibody diversity:
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
Describe how each B cell produces immunoglobulin of a single antigen specificity.
- 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
Indicate the mechanisms by which auto-reactive B cells are prevented from causing autoimmune disease.
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.
Where does central tolerance occur?
Primary lymphoid organ
(B cells = bone marrow)
(T cells = thymus)
Define central tolerance (as related to B cells)
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.
Define peripheral tolerance (related to B cells)
Tolerance induced to antigens outside the bone marrow
What is somatic recombination?
DNA recombination that occurs between gene segments. It generates a complete exon composed of VJ(D) segment encoding the variable region of the gene
What is junctional diversity?
Diversity created during the process of gene rearrangement by addition or removal of nucleotides at the junctions between gene segments