Development of the B-cell

 

Development of the B-cell

¢  In humans, the immune system begins to develop in the embryo.

¢  The immune system starts with hematopoietic (from Greek, "blood-making") stem cells.

¢   Stem cells differentiate into

  1. WBC :

            Ø    Granulocytes

            Ø    Monocytes

            Ø    Lymphocytes.

  1. Cells not involved in immune function, such as

            Ø    Erythrocytes (red blood cells)

            Ø   Megakaryocytes (for blood clotting).

  1. Stem cells continue to be produced and differentiate throughout your lifetime.
  2. By the time a baby is born, the immune system is a sophisticated collection of tissues that includes:
    1.  the blood
    2. lymphatic system
    3. thymus
    4. spleen
    5. Skin
    6.  Mucosa

 



B- Cell Development

¢  B lymphocytes –B originates from Bursa of fabricus-an organ in which avian B-cells mature from

¢  In human, B lymhocytes develop initially in the fetal liver and transfer to  bone marrow around 12 -16th week of fetal life.

¢  From then on, the bone marrow is the only site of B-lymphocyte generation.

 

B lymphocyte

¢  Pro B cells- (bone marrow)

¢  Pre- B cells- (bone marrow)

¢  Immature B cells- (bone marrow)

¢  Mature B cell – (lymph node, Spleen)

 

 

1)    Pro B cells- bone marrow-

1)    Successful rearrangement  of heavy  chain: there is D-J  and V-DJ rearrangement

2)    Characterised by presence of Ig heavy chain protein of the u class in the cytoplasm,

3)    Natural selection –Negative selection: Removal of a cell with undesirable contributes.

          Generation of Ig gene rearrangement that do not lead to productive expression of heavy       and light chain.

       4). negative selection - 75% of the cells are killed before they leave the bone  marrow

         Immunoglobulin  molecules that  recognize and bind to self antigens, will undergo         apoptosis

 

2. Pre- B cells-    bone marrow

1)    – VDJ genes rearranged (heavy chain)

2)    V-J genes rearranged(light chain)

3)    Express Ig light chain protein,

4)    Contain intracytoplasmic IgM heavy chain, they synthesize mu heavy chains but without light chain partners,

5)     B cells  able to bind and internalize antigen, & present the antigen to T cells and will receive a positive signal for expansion.

 

3. Immature B-cells -migrate from the bone marrow to spleen

1)    At this stage B cell express sIg composed of µ and δ heavy chains, which express surface IgM and IgD.

2)    Negative selection of B-cells, a minority of these cells survive, deletion occurs in the spleen.

3)    Cells not receiving appropriate signals in the lymph node germinal centre are lost

4)    Selection of B cells with highest affinity for antigen-which happens naturally by competition for antigen

5)    class switching- Alternative heavy chains are now selected. B-cells selects one of the major classes or sub-classes of Ig heavy chain, memory B cells  can give a swift, specific high affinity, class switched 20 response.  memory B cells and plasma cells are constantly being replenished . committed to a specific antigen. Only one antigen binding specificity of Ig is produced per B cell-composed of variable region of light and heavy chain (VL, VH)

6)    Surface IgD is lost from cell after antigen encounter (IgD signifies virgin B cell), the virgin cell matures

 

4. Mature B cell

¢  Lymph node

¢  Has antigen specificity

¢  VDJ C rearranged (Heavy chain)

¢  VJC  rearranged (light chain)

¢  IgM and IgD on the surface- the cell enters circulation and binds specific antigen in lymphoid tissue

 

 

 

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