Lec 40: Development of B cells

Question 1

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

Answer 1

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

• 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

Question 4

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

Answer 4

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.

Question 5

Where does central tolerance occur?

Answer 5

Primary lymphoid organ

(B cells = bone marrow)

(T cells = thymus)

Question 6

Define central tolerance (as related to B cells)

Answer 6

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.

Question 7

Define peripheral tolerance (related to B cells)

Answer 7

Tolerance induced to antigens outside the bone marrow

Question 8

What is somatic recombination?

Answer 8

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

Question 9

What is junctional diversity?

Answer 9

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