Similar to other blood cells, lymphocytes are generated from Stem Cells (SCs) in the bone marrow. Lymphocytes and Natural Killer cells (NK) raise from myeloid line of Haematopoiesis.
Lymphocytes differentiate and mature in thymus (T cells) and bone marrow (B cells). Lymph nodes, spleen, and RES are also involved in this process. Majority of peripheral blood lymphocytes are T cells (70%).
Having produced in the bone marrow, they migrate to other lymphoid organs and parts of the body. Since the thymus is the place for education of T cells, both bone marrow and thymus are called as primary lymphoid organs. B lymphocytes are formed within the bone marrow and undergo their development there. While B cells are educated in the bone marrow, T cells use another place for this aim. Then, T and B cells migrate to secondary lymphoid organs as shown below:
Primer and Seconder Lymphoid Organs
They travel amongst body sides, which they were generated, blood and lymphatic circulation. When they arrive in any lymph node, they prefer staying in different zones due to their types. B cells take place in germinal centers, T cells move to paracortical zone. When T and B cells are activated by receiving appropriate signals via their surface receptors, they are gathered in medulla zone to leave for their mission in peripheral tissues.
Lymphocytes are divided into two main groups as B and T cells. They show differences on their surface. T cells bear T cell receptors (TcR) and B cells represent B cell receptors (BcR) on their surface.
As shown above, BcR is a similar molecule to an antibody produced and secreted by B lymphocytes with minor modification in tail structure (Fc part). On the other hand, TcR is a different molecule associated with CD3 as signaling part of the receptor.
BcR recognize appropriate soluble antigen (Ag) via its Fab part. However, in order to recognize, TcR needs processed antigen peptide represented by MHC (Major Histocompatibility Complex) molecule of an antigen presenting cell (APC).
The lymphoid stem cells differentiate into B cells in bone marrow. B-cells precursors mature, differentiate into immuno- competent B-cells with a single antigen specificity. Immature B-cells that express high affinity receptors for self antigens, die or fail to mature -i.e negative selection or clonal deletion.This process induces central self tolerance and reduces risk for autoimmune diseases.
Immature B cells express only IgM receptors on the surface. Mature B cells express IgM, IgD molecules on surfaces.
IgM and IgD molecules serve as receptors for antigens
Memory B-cells can express IgG or IgA or IgE on the surface.
B-cells bear receptors for Fc portion of IgG and a receptor for C3 component of the complement system. They express an array of molecules on their surfaces that are important in B-cells interactions with other cells such as MHC II, B7 and CD40
B cells have the following functions:
1) They interact with antigenic epitopes, using their immunoglobulin receptors
2) They receive inducer signals from some cytokines
3) They subsequently develop into plasma cells, secreting large amounts of specific antibody
4) They circulate as memory cells
Differences between naïve and memory B cells are shown in the table below:
Today, we know that B cells have at least two different types, B1 and B2 cells.
B1 Cells are CD5+, and mainly seen in fetal and perinatal ages of life. They have very long life span and produce high levels of IgM, in particular autoantibodies. These cells involve in some malignancies.
On the other hand, B2 cells are CD5-. They can be seen during life time and are short period living cells. They produce all Ig isoforms and involve in adaptive immune response.
They express TcR on the surface, made of 8 transmembrane proteins. Two chains recognize antigen peptide processed by APCs (a + b chains or d + g chains). Therefore, we call T cells TcR a b or TcRdg cells in regard to the chains. Other 6 chains (g, d, e (x2), z (x2) chains) form CD3 molecule and transduce signal into the cell.
T-lmphocytes migrate from bone marrow to enter thymus. In the outer cortex of thymus, T-lymphocytes acquire specific receptors (TCRs). This receptor commits lymphocyte to a single antigen specificity When they encounter an appropriate signal from an antigen peptide, they responding by proliferation and production of a clone of cells (clonal selection). They differentiate to express CD3, both CD4 and CD8 co-receptors (double positive cells). In the medulla of thymus, TCRs recognize MHC molecules, loaded with normal self-peptides (p-MHC). TCRs capable of binding with low affinity to p-MHC will receive positive selection signals to divide and establish clones. TCRs that bind too strongly to p-MHC undergo (negative selection) and die. This selection process will eliminate the potentially most harmful self reactive T-cells (central self tolerance).
Immature T-cells express both CD4 and CD8 (DP). As they mature, T-cell with TCRs that have affinity to bind to MHC class II will become helper T-cells with CD4 molecule only (single positive, SP). On contrary, T-cell with TCRs that have affinity to bind with MHC class I will become cytotoxic T-cells with CD8 molecule only (Single positive, SP).
Mature positively selected T-cells are MHC restricted. CD4 T-cells are MHC II restricted and only recognize specific foreign peptide only when they are presented in association with specific MHC II molecules. CD8 T-cells are MHC I restricted and recognize specific foreign peptides only when they are presented in association with specific MHC I molecules.
Then, we can classify T cells now.
T Cells subtypes:
1) CD4 Helper T cells (Th: CD4+)
Starting with Th cells, Th lymphocytes recognize antigen on the surface of APC in association with class II MHC molecules. They are activated and secrete several cytokines.
There are two main subsets of Th cells (Th1 and Th2). The two subsets are differentiated on basis of the cytokine they produce.
Th1 produce mainly cytokines of cellular mediated immunity) CMI and inflammation, e.g. IFN-γ, TNF- β, IL-3 and IL-2.
Th2 produce mainly cytokines that stimulate B-cells and suppressor cytokines, e.g. Il-4, IL-5, IL-6 and IL-10.
2) CD8 Cytotoxic T-lymphocytes (Tc: CD8+, CTLs)
They constitute 35% of peripheral T-cells. CTLs recognize antigen on surface of target cells (infected APC or other infected nucleotid cell) in association with MHC-I . They are activated and kill the virus infected cell or tumour cell.
Finally, we can now explain the differences between T and B cells in regard to their antigen recognition. Antigen receptors of B cells are antibodies. On contrary, TcRs serve for T cells. Both receptors, TcR and BcR, require VDJ recombination. BcR is formed by 2 heavy and 2 light chains in addition to Ig-a and Ig-b transducing signal. TcR has ab or dg heteromer associated with CD3 molecule as signal transducer. BcR recognizes soluble antigens, but TcR recognizes peptide antigens presented by APCs. This comparison was shown below.
As to main markers of T and B cells, they were given below. Red lines is for B cells, and green lines is for T cells. Then, we can observe their phenotypes in respect to their surface molecules in research and clinical laboratories.
Lymphocytosis >4.0 x 109/L adults & >10.0 x 109/L kids
II. Secondary (reactive)
Stress (transient stress lymphocytosis)
Mononucleosis syndromes (EBV, CMV, rubella)
Bordetella pertussis (whooping cough)
Lymphopenia <1.0 x 109/L adults & <2.0 x 109/L kids
I. Congenital immunodeficiency
II. Acquired causes
Infectious disease i.e. -HIV
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