Generation, Activation and
Differentiation of Lymphocytes
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Immunology: B and T Lymphocyte Generation, Activation, and Differentiation - Prof. Yusuf, Summaries of Immunology
An in-depth analysis of the development process of b and t lymphocytes, from their generation in the bone marrow and thymus to their activation and differentiation into plasma cells, memory cells, and various effector cells. The role of antigens, mhc molecules, co-stimulatory molecules, and cytokines in the maturation and activation of these immune cells.
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2023/2024
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Generation, Activation and
Differentiation of Lymphocytes
B cell generation, Activation and
Differentiation
(^) The development process that result in production of plasma cells and memory B cells can be divided into three broad stages (^) Developmental process: (^) Generation of mature, immunocompetent B cells ( maturation ) (^) Activation of mature B cells when they interact with antigen, & (^) Differentiation of activated B cells into plasma cells and memory B cells
Fig. 2. Overview of B cell maturation Source : Abbas – Kuby. Immunology 2007 5th^ ed). 4
Progenitor B Cells Proliferate in Bone Marrow
Pro-B cells bind to stromal cells by means of an interaction between VCAM-1 on the stromal cell and VLA-4 on the pro-B cell. (^) This interaction promotes the binding of c-Kit on the pro-B cell to stem cell factor (SCF) on the stromal cell, (^) which triggers a signal that stimulates the pro-B cell to express receptors for IL-7. (^) IL-7 released from the stromal cell then binds to the IL- receptors, inducing the pro-B cell to mature into a pre-B cell. Proliferation and differentiation eventually produces immature B cells.
Ig-Gene Rearrangment
(^) B-cell maturation depends on rearrangement of the immunoglobulin DNA in the lymphoid stem cells (^) First to occur in the pro-B cell stage is a heavy-chain D H-to-JH gene rearrangement; this is followed by a V H -to-D H J H rearrangement Upon completion of heavy-chain rearrangement, the cell is classified as a pre-B cell. (^) Continued development of a pre-B cell into an immature B cell requires a productive light-chain gene rearrangement.
Heavy-Chain DNA Undergoes V-D-J Rearrangements
Source : Abbas – Kuby. Immunology 2007 5th^ ed). 10 Overview of B-cell development
Comparison of naïve and memory B cells
Source : Abbas – Kuby. Immunology 2007 5th^ ed). 14
(^) T cell-independent (TI) antigens: (^) Can activate B cells without direct participation by TH cells (^) This response to TI antigen Usually involves simple lipids, Antibody production is weaker, No memory cells are formed, and IgM is the predominant antibody secreted, (^) Reflects low level of class switching
B cell activation and differentiation
Memor y B cell
(^) Primary response
- (^) long lag period
- (^) short plateau, and then a decline
- (^) IgM is the first antibody class
- (^) followed by a gradual switch to other classes, such as IgG (^) secondary response
- (^) shorter lag time
- (^) longer plateau phase
- (^) slower decline than the primary response
- (^) Mostly IgG and other isotypes are produced in the secondary response rather than IgM, and
- (^) the average affinity of antibody produced is higher