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B lymphocytes and antibody production

B lymphocytes and antibody production. B LYMPHOCYTES:. are responsible for the generation of specific humoral immunity (production of antibodies) - are under the regulation of T cells. DIFFERENTIATION (antigen independent) :. in bone marrow changes in cell membrane molecules and

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B lymphocytes and antibody production

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  1. B lymphocytes and antibody production

  2. B LYMPHOCYTES: are responsible for the generation of specific humoral immunity (production of antibodies) - are under the regulation of T cells DIFFERENTIATION (antigen independent): in bone marrow changes in cell membrane molecules and in morphology precursor  pre B  mature B  plasma cell rearrangement of genetic information coding receptors for antigen (BcR) BcR complex membrane expression

  3. RECEPTORS FOR ANTIGEN ON B CELL (BcR) same genetic rules as for TcR (V, D, J recombination, C) limited selection for „self“ specific recognition of unprocessed, native antigens (spatial conformation) somatic mutation changes of BcR in the presence of antigen (affinity maturation)

  4. S S S S S S S S S S VH DH JH Cm C C C 4 C1 C 3 C 2 C 1 C 2 C  ORGANISATION OF IgH LOCUS NUCLEOTIDE SEQUENCES BETWEEN GENE SEGMENTS (12-23 RULE ) 12 bp Vk CACAGTG ACAAAAACC Jk GTGTCAC TGTTTTTGG 23 bp

  5. REARRANGEMENT OF V-J GENE SEGMENTS (LIGHT CHAIN) J1 V2 V4 V1 V2 V3 J2 J3 9 9 RAG -1,2 RAG -1,2 12 23 7 7 V1 V2 J2 J3

  6. DIFFERENTIATION OFB CELLS (antigen independent): HLA II HLA II (CD 34 ) CD 19 rearrangement TdT CD 10 cCD 79a c CD 19 HLA II CD 19 MATURE B CELL Y CD 79a BcR CD 79b

  7. DIFFERENTIATIONB CELLS (antigen driven): takes place in secondary organs of immune system lymph node, spleen, mucosa the site of B cell- antigen encounters proliferation of B cells, terminal differentiation germinal center primary production of antibodies immunoglobuline molecules are soluble forms of BcR

  8. Y HLA II CD 79a BcR CD 19 CD 79b Y CD 38 Y DIFFERENTIATION INTO PLASMA CELL antigenic stimulus TH2 help B cell somatic mutation izotypic switching Y Y Y Y immunoglobulins solubile forms BcR

  9. B- CELLS - RECOGNITION OF ANTIGEN(BcR) C3d Ag CD 23 sIgM H H L L CD 19 CD81 CD79 a,b TAPA-1     ITAM ITAM ITAM ITAM ITAM Lyn B - cell kinases

  10. SECONDARY LYMPHATIC FOLICLE B-cells marginal zone plasma cells mantle zone germinal centre mutation og genes for Ig affinity maturation memory B-cells

  11. T- B CELLS INTERACTIONS intimate cell-cell contact B cells are able to process and present antigens to T cells cognitive interactions through BcR costimulatory interactions cytokines regulated

  12. T CELLS, B CELLS INTERACTIONS IL - 4 FceR II. CD 21 TH2 CD40L CD40 B cell plasma cell TCR Y Y costimulation Y Y Y Y Y Y Y Y IL - 13 specific antibidies

  13. ISOTYPIC SWITCHING primary antibodies are IgM isotype (C is the nearest to VDJ) other isotypes are generated after additional gene rearrangement regulated by T cell system: cytokines: IL-4 T-B cell contact: CD40L  CD40 development of germinal center

  14. Isotypic switching S S S C 1 S S C  C1 C 3 C 1 C  S C 2 S S C1 C 3 S C C 4 Cm C 2 C S S S C 4 Cm S S S V D J Ce Ca2 C C 2 promotor enhancer V D J

  15.  Krejsek, 2004

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