Development of immune repertoire

Maturation of lymphosytes requires

IL-7 (growth factor) produced by stromal cells in bone marrow, expression of antigen receptor genes, selection of lymphocytes that are useful

stages of lymphocyte maturation

immature lymphocyte (IL7 growth factor) → prelymphocyte in primary lymphoid organs (bone marrow/thymus) → mature lymphocyte in peripheral tissue

see self antigens

immature lymphocytes must

positive selection

expression of complete antigen receptor, has weak (self) antigen regocnition

negative selection

expression of complete antigen receptor, has strong (self) antigen recognition (these cells can cause autoimmute disease)

B-cell antigen receptors w/ Ig heavy chain

V, D, and J (variable regions), and C (constant region)

T-cell receptors w/ TCR-beta chain

V, D, and J (variable region), and C (constant) (T cell receptors)

creating diversity of antigen receptors

combinational diversity (mix & match) and junctional diversity (add or delete)

IgM heavy chain pattern

V+D+J+C(mu)

IgG heavy chain pattern

V+D+J+C(gamma)

Light chain patterns for IgM and IgG

V+J+C (will not be changed during the lifespan of a B cell clone)

How Ig forms are expressed

alternative splicing

RAG-1 and RAG-2

combinational diversity genes (cause recombination; animals that lack these genes will lack T and B cells)

RNA processing (Add or delete)

junctional diversity mechanism

gene conversion

pseudogenes incorporated into the V region

the thymus (IL-7 promotes proliferation)

where T lymphocytes mature

allelic exclusion

makes it so that the cell can only recognize one antigen

bone marrow

initial stage of B cell maturation

Peyer’s patch (ruminants), bursa of Fabricius (birds), spleen (humans)

final stage of B cell maturation

peritoneum mucosal sites

Site of B-1 cell maturation

B-2 Cells

Conventional B cells

1st checkpoint of B cells (pre-B cells)

if no mu protiein = cell death; need recombination of IgH and recombintaion og Ig at light chain

2nd checkpoint of immature B cell

has a complete IgM receptor (BCR); receptor functions properly

3rd/ final checkpoint of B cell maturation

has the co-expression of IgM and IgD (due to alternative splicing)