Immunology - Lecture 7 - Cells of Adaptive Immunity

- Associated with B Cells
(membrane Immunoglobulins)
- CD79a/b anchors B-cell receptors to the membrane

Variable and Joining (V and J)

V, D, J
Variable, Diverse, Joining

process of constructing a variable region of immunoglobulin
- D& J combine first, and then V.

successful rearrangement of heavy chain variable region on one chromosome, inhibits somatic recombination of heavy chain variable region on the other member of chromosome pair

- Transcription of RAG1 and RAG2
- CD79a/CD79b are linked to intracellular signaling mechanism
- no immunologically relevant molecules present

- Pre-BCR is expressed on cell surface
- CD79a/Cd79b is also on cell surface
- initial transcription of μ heavy chain

- allelic exclusion - when getting chromosomes from one parent, must inactivate the other

- pre-BCR -> BCR (IgM) = fully functioning Ig
- BCR has 2 μ heavy chains
- initial transcription of kappa and lambda light chains
- tolerance induction

- Alternative Splicing - can produced different constant regions of cell surface antibodies

- Mature B-cells leave bone marrow, enter blood stream, migrate to peripheral lymphoid tissue, recirculate if don't encounter antigen in secondary lymphoid tissue
-cell surface has Cd40, cd21 cd81 cd45

vascular molecules. control homing of B cells

process by which hnRNA encoding variable region (VDJ) of heavy chain is spliced to either μ or δ constant region to form IgM or IgD

CD79a/CD79b
mIg (membrane immunoglobulin)

hematopoiesis

antigen bind contact site (other end of epitope

non-covalent

CD40 Ligand

- B cell clonal expansion
- Isotype Switching
- Affinity maturation
- Differentiation into plasma cells and memory cells

IgG.
binds to FcγRIIB - low affinity receptor

- Secondary
- can occur anywhere in body (outside of secondary lymphoid tissue)
- Higher Antibody titer (much more progeny ~1 log greater)
- less lag for:
affinity maturation, differentiation to plasma cells and migration to follicle cells,

enhances the immune response
- added to vaccines

polyclonal activator. can trigger proliferation of many clones of lymphocyte B.
-

- Multiple germline genes
- Combinatorial association
- Junctional Diversity
- Random selection of the light and heavy chains

adhesive molecules on B-cells that interact with addressin (in high endothelial venules) to mediate exit from blood to peripheral lymph nodes

- mutation on BTK kinase
- BTK kinase plays a critical role on B cell activation, differentiation and proliferation
- initial defect occurs between the pro-B and pre-B transition

Diabetes Mellitus (Type I)

Ankylosing Spondylitis

- stomach pains
- Coeliac Disease

At afferent lympatics rather than high endothelial venules (HEV’s).

Because they lack L-selectin. (needed to go from blood to lymph at HEV)

CD19
CD40/CD40 ligand
Btk kinase

They are antigens that don’t need a T-cell for them to be recognized by B-cells.

IgM is produced.

Type I and Type II

Type I - only IgM. no isotype switching

Type II - some isotype switching

Mu and Delta are excised, leaving alpha, epsilon or gamma heavy chain constant regions.

B cells express antigen specific antibodies as cell surface receptors.

Plasma cells secrete antibodies.

CD40/CD40 ligand interaction

Clonal expansion.
Activated B cells and T cells migrate to the primary follicles where enhanced proliferation of B cells leads to the formation of germinal centers

L-selectin, an adhesive molecule that is present on the B-cell.

It interacts with vascular addressin molecules on the high endothelial venules (HEV).

All mIg present on the surface of any one B cell will have the same heavy chain variable region

Tdt.
terminal deoxynucleotidyl transferase-
A template independent DNA polymerase

The heavy chains are known as mu and delta.
The light chain constant regions are either kappa or lambda.

The heterodimer CD79a/CD79b.
Two identical heavy chains and two indentical light chains linked by a disulfide bond.
Each chain is made up of a variable and constant region.