Lecture 9 – B Cell Function, Effector
Mechanisms and Differentiation
Overview of B Cell Response
- Naïve B cells:
o Memory cells.
Long life.
Same BCR as parents.
o Plasma (effector) cells (plasma blasts).
Live for a few days at a time.
Secrete many antibodies (2000 per second).
All lymphocytes come from a Haematopoietic Stem Cell (HSC).
HSC
Common myeloid Common lymphoid
progenitor progenitor
Myeloblast Lymphoblast
Erythrocyte
Platelets T Lymphocyte B Lymphocyte
Main role is to produce antibodies.
B in B cells is from the Bursa of Fabricus, and the T in the T cell is from the Thymus.
Bone Marrow Maturation of B Cells
Pro B Cells
- Receive survival signals from the bone marrow stromal cells.
- Switches on Ig alpha/ Ig beta (CD79A/CD79B).
- Cells express Tdt and RAG.
- Genetic recombination occurs DH-JH then VH – DHJH.
- No BCR is expressed.
, Pre-B Cells
- Synthesis of surrogate light chain pairs with the heavy chain to form a pre-BCR.
- Comprises of 2 proteins.
- If the signal is received the cell will continue to produce immature B cells, and if it is not
received the cell will undergo apoptosis.
Immature B Cell
- Loses expression of the surrogate light chain.
- Rearranges the light chain genes (kappa or lambda).
- Light chain proteins are produced, and they combine with the heavy chain.
- Expression of the mature BCR on the cell surface [initially IgM].
CHECKPOINT 1: Pre-B Cell to Immature B Cell
Differentiation only occurs if the signals are received through the pre-BCR. spontaneously
aggregates without the antigen and signals through Ig alpha/Ig beta, tells cells to:
o Don’t make heavy chain from the other allele (allelic exclusion).
o Start rearranging light chain genes.
o Stop making pre-BCR.
CHECKPOINT 2: Survival of Immature B Cell
In bone marrow IgM on the surface supplies a survival signal without this the cell dies.
2 checkpoints ensure that only cells expressing a heavy and light chain IgM survive to an
immature B cell.
B cell development to this point is independent of an antigen.
90% of B cells die before leaving the bone marrow.
B Cell Negative Selection
Autoimmunity is prevented by negative selection.
- Cells with a high avidity for proteins in the bone marrow either die or rearrange V region
genes.
Differentiation of B Cells Outside the Bone Marrow
- Immature B cells upregulate IgD on the surface and become IgM + IgD + mature B cells
(circle the body).
- Naïve as they have never seen the antigen, it binds to their surface IgM and IgD.
B Cell Antigen-Induced Activation
- Antigens are drained from tissueslymph, bloodspleen.
- B cells circle the lymph/blood= increases chance of meeting an antigen. Antigen could be T-
dependant or T-independent.
T-Independent Antigens
Cross link receptors to activate B cells without help from T cells:
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