Bcell activation , differentiation and memory

Immunology - B cell activation ,differentiation and memory

1. TOPIC : B cell activation, differen tiation and memory By : Akshita Mengi roll no. : 12

2. B CELL Type of lymphocyte involved in humoral immunity of adaptive response system as they differentiate Into plasma cells and antibody . Also considered as antigen presenting cells as these can detect the antigen present on surface of bacteria. These generate and mature in bone marrow hence the name b cell . Have receptors on surface Known as b cell receptors.It is a macromolecular complex that is built with help of IgM and IgD . Because of presence of receptors on surface they can detect the antigens that occur on surface of pathogen.

3. They can express MHC –II . Have surface marker or identification marker CD-19 . Antibodies at suface – IgM and IgD .

4. B cell development B-cells develop from hematopoietic stem cell (HSCs) that originate from bone marrow. HSCs first differentiate into multipotent progenitor (MPP) cells , then common lymphoid progenitor (CLP) cells. From here , their development into B-cells occurs in several stages each marked by various gene expression patterns & immunoglobulin H chain and L- chain gene loci arrangements.

5. B CELL ACTIVATION. B cell activation occurs in the secondary lymphoid organs such as spleen and lymph nodes. After B cell mature in the bone marrow, they migrate through the blood to secondary lymphoid organs , which receive a constant supply of antigen through circulating lymph. At the secondary lymphoid organ, B cell activation begins when the B cell binds to an antigen via its BCR . Humoral or antibody response is generated by antigen stimulated B cells, which terminally differentiate into antibody forming plasma cells and memory cells. Some antibody response requires T –cell help and some are independent of T cell help.

6. TYPES OF B CELL ACTIVATION. B cell activation are of two types. T cell dependent activation of B cell . T cell independent activation of B cell .

7. T- CELL INDEPENDENT ACTIVATION OF B- CELL. Such humoral response is independent of T –cell cooperation. Although the activation is independent of T cell, cytokines produced by T cells can amplify their responses . The antigens that activate B cells directly are are called T independent or T( ind ) antigens. T( ind ) antigens are products of bacteria such as capsules, endotoxins , flagellar proteins or lipopolysaccharide of Gram Negative bacteria. The T cell independent antigens directly bind to the B cell by cross linking to their BCR. This leads to activation, proliferation and differentiation of B cells directly into AFC and memory cells.

8. Crosslinking or clustering of BCR by microbial surface. (Signal 1 ) No involvement of T cell. Antigens are called thymus independent antigens. This antigen has multiple identical epitope . TLR can also work . (Signal 2 ) No memory cells are formed . Antigens can be polysaccharides,bacterial cell wall component , glycolipid , nucleic acid Epitope = bacterial cell surface molecules that an antibody present on surface of b cell recognizes .

9. T CELL DEPENDENT ACTIVATION OF B – CELL In T cell dependent activation, the antigen activation of B cell with cooperation of T cells is called T - cell dependent B cell activation. The antigens are known as T dependent antigens Td such as erythrocyte and proteins. In T cell dependent activation , the first encounter with an antigen is imperative for formation of T cells and B cells to produce antibodies and in development of memory T and B cells.This is known as primary response. Subsequent encounter with same antigen leads to a secondary immune response.

10. T cell dependent activation Signal1& 2

11. The cellular events that occur in primary response of T cell dependent activation is summarised as follows :- Capture of antigens by APCs such as macrophages and dendritic cells, processing of protein antigen into peptides and display of antigenic peptides over the surface of APCs in Association with MHC – II molecules. Interaction of peptide antigen on MHC – II molecules with Th cell bearing an appropriate TCR. Additional interaction between the costimulatory molecules and adhesion molecules. Paracrine stimulation of Th cells by lymphokines synthesized by APCs such as IL-1. Autocrine stimulation of Th cells by IL-2 , IL-4 and IL- 7. Release of other lymphokines like IL-4 , IL-5 and IL-6 by activated Th cells. Lymphokine mediated growth and clonal proliferation of resting B cell by IL-4 and IL- 5. Differentiation of B cells by IL-6 and INF-Gamma into AFC and memory cells. Synthesis of specific isotype antibodies.

12. BIOCHEMICAL EVENTS IN B CELL ACTIVATION. The transmembrane molecules the BCR on B cells like TCR on Tcells have short cytoplasmic tails to initiate B cell activation. Other molecules are associated with BCR in transducing signals within the the B cells . Ig alpha and Ig beta in particular are associated with BCR and have Intracellular Tyrosine Activation Motifs ( ITAMs), which are phosphorylated tyrosine kinases. These kinases act early in B- cell activation and initiate B- cell signalling cascade. Cytokines like IL- 2 and the physiologic ligand CD40 on B cell and CD40 L on T cell is second signal for B cell activation. Other molecules CD19, CD 21 and CD 81 are probably involved in amplification of signal transduction. Other cytokines produced by Th cells induce B cell differentiation into plasma cells and memory cells.

13. During differentiation certain changes occur in b cell , certain reactions occurs to produce variety of antibodies . Protein factors are produced . Translation process starts . Change in morphology , cytosolic content increases ,cell takes bigger shape with nucleus at the end because they require wide area for translation.

14. Class switching

15. B CELL DIFFERENTIATION. After activation of B cells there occurs proliferation and then differentiation of B cell into :- Plasmablast Plasma cells Regulatory B cells The long lived memory B cells .

16. PLASMABLAST. A short lived, proliferating antibody - secreting cell arising from B cell differentiation . Plasmablasts are generated early in an infection and their antibodies tend to have a weaker affinity towards their target antigen compared to plasma cell .

17. PLASMA CELLS. A long lived, non proliferating antibody secreting cell arising from B cell differentiation. There is evidence that B cells first differentiate into a plasmablast like cell, then differentiate into a plasma cell. Plasma cells are generated later in an infection and compared to plasmablasts have antibodies with a higher affinity towards their target antigen due to affinity maturation in the germinal centre (GC) and produce more antibodies .

18. REGULATORY B (BREG) CELL. An immunosuppressive B cell type that stops the expansion of pathogenic, pro-inflammatory lymphocytes through the secretion of IL-10, IL-35, TGF- beta. Also it promotes the generation of regulatory T (Treg) cells by directly interacting with T cells to secure their differentiation towards Tregs . There is evidence showing that nearly all B cell types can differentiate into a Breg cell through mechanisms involving inflammatory signals and BCR recognition.

19. MEMORY B CELL. Dormant B cell arising from B cell differentiation . Their function is to circulate through the body and initiate a stronger, more rapid antibody response (known as the the anamnestic secondary antibody response) if they detect the antigen that had activated their parent B cell (memory B cells and their parent B cells share the same BCR, thus they detect the same antigen).

20. B CELL MEMORY. B cell memory is a type of B lymphocytes that forms part of the adaptive immune system. These cells develop within germinal centres of the secondary lymphoid organs . Memory B cells circulate in the blood stream in a quiscent state, sometimes for decades . Also known as memory B-cell (MBC) . Function :- Function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. Memory B cells have B cell receptors (BCRs)on their cell membrane, identical to the one on their parent cell that allow them to recognise antigen and mount a specific antibody response.

21. LIFE SPAN OF MEMORY B CELL. Memory B cells can survive for decades which gives them the capacity to respond to multiple exposures to the same antigen . The long lasting survival is hypothesized to be a result of certain anti- apoptosis genes that are more highly expressed in memory B cells than other subsets of B cells. Additionally,the memory B cell does not need to have continual interaction with with the antigen nor with T- cells in order to survive long term.