Lecture # 7 B Cell Development Flashcards
What constitutes (or makes up) the pre-BCR?
heavy chains, Vbre, and lambda 5 (all three make up the surrogate light chain)
What are the two checkpoint stages of B cell development?
The pre- B cell stage and the immature B cell stage
Central lymphoid organs
Specialized tissue where lymphocyte development takes place (Bone marrow for B Cells)/ (Thymus for T Cells)
Peripheral lymphoid organs
Specialized lymphoid organs where mature lymphocytes reside and circulate in the blood (spleen, lymph nodes, mucosal lymphoid tissue)
Stages of B- Cell maturation
1) Stem cell 2) pro lymphocytes 3) pre lymphocytes 4) immature lymphocyte 5) Mature lymphocyte
Which stage in B cell development is Antigen dependent?
The second checkpoint, immature B - cell. Tests against self antigens
Why are stromal cells important in B cell development?
stromal cells have FLT3L, which B cell progenitors bind and cause them to differentiate to become B cells. Stromal cells also produce IL-7
What two receptors are present on the surface of B-cell progenitors?
FLT3 and IL-7 receptors
Why is IL-7 production important in B-Cell production?
IL-7 promotes the expression of E2A, E2A promotes the expression of EBF, EBF promotes the production of Pax-5 which are all important in B-cell development. Cause B cell to express CD19, Ig alpha
What are events that mark the transition from the pro-B to pre-B cell?
upregulation of RAG and TdT. Goes from unrecombined (germline) DNA to Recombined H chain gene (VDJl u mRNA
What surface marker is developing during the pro-B stage?
CD43+, CD10+, but most importantly CD19+
BTK
Bruton’s Tyrosine Kinase. Deficiency in this gene cause lack of development of B cells. BTK is activated downstream of Pre-BCR to mediate proliferation and survival.
X- Linked Agammaglobulinemia
Inherited inability to make antibodies; no tonsils (because the tonsils are just a big lymphoid organ that house b cells); deficiencies in b cells and their products
CD19 vs CD3
CD19 (B-cell) CD3 (T Cell)
When does D-J rearrangement of H chain occur?
Occurs in early pro-B stage.
When does V-DJ rearrangement occur?
late pro-B on one allele (allelic exclusion) Successful rearrangement produces intact heavy u chain. Post VDJ pro B-cell becomes pre-B cell
What happens to cells that do not produce an intact u H chain?
They are eliminated
Why are checkpoints needed?
1) VDJ is random, imprecise and can result in unsuccessful rearrangement. 2) Tests for functional receptor
The light Chain
The light chain is produced after the heavy chain is produced. The light chain and the heavy chain are produced on different chromosomes.
Where does central tolerance occur?
The central lymphoid organs (In the bone marrow) . High avidity B cells either undergo receptor editing or apoptosis.
Clonal deletion
Occurs when BCR bind strongly to self antigen-multivalent Ag cross-links BCR. Cell gets a very strong signal through IgM at the immature stage and dies.
Clonal anergy
Occurs when BCR soluble self antigen-still cross-links BCR down regulates IgM and cell cannot be activated. Cell gets moderate signal and dies later.
What is the receptor on B-cells? T-cells?
B cells CD19/ T-Cells CD3
Clonal Ignorance
occurs when BCR binds soluble self antigen with low affinity, monovalent antigen—self reactive cell receives weak or no signal- cell still exists and in many cases does not encounter Ag.
