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Lecture notes

B cell function, effector mechanisms and differentiation

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Lecture notes on B cells, their function, effector mechanisms and how they differentiate

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  • February 24, 2022
  • 5
  • 2021/2022
  • Lecture notes
  • Sarah buchan
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biomedicalscience4
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 tissueslymph, bloodspleen.
- 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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