浙江大学医学免疫学经典课件免疫9、13-B细胞

1、Lie Wang (汪洌）,浙江省杭州市浙江大学紫金港校区 医学院科研楼A810-814 医学院免疫学研究所,B lymphocytes and Humoral Immune Response,The discovery of B cell immunity,1954 - Bruce Glick, Ohio State University Studies on the function of the bursa of Fabricius, a lymphoid organ in the cloacal region of the chicken,Bursa was later found t

2、o be the organ in which antibody producing cells developed antibody producing cells were thereafter called B cells Mammals do not have a bursa of Fabricius,Origin of B cells and organ of B cell maturation,After birth, development continues in the bone marrow,B cell development starts in the foetal l

3、iver,B cell development in the bone marrow,Bone Marrow provides a MATURATION 2. produce polyreactive Ab clearance of denatured self components; 3. produce auto-Ab, thereby participating in the pathogenesis of some autoimmune diseases.,Comparison of B-1 and B-2 B cell properties,Property B-1 cells B-

4、2 cells N regions Few Extensive V region repertoire Restricted Diverse Location Peritoneum/pleura Everywhere Renewal Self renewal in situ Bone marrow Spontaneous Ig production High Low Isotypes IgM IgM/G/A/D/E Carbohydrate specificity Yes Rarely Protein specificity Rarely Yes Need T cell help No Yes

5、 Somatic hypermutation of Ig No High Memory development No Yes,Specificity cytokine (e.g. IL4) signals also contribute FasL triggers Fas - BCR signaling protects from apoptosis T cell derived cytokines influence differentiation, isotype switching: IL2, IL6 promote differentiation IL4 - IgG1, IgE IFN

6、g - IgG2a, IgG3 TGFb and IL5 IgA Many other molecules involved in T-B interactions e.g. ICAM1/LFA1, ICOS/ICOSL, CD30/CD30L, CD27L/CD27, OX40L/OX40, .,d. Th cells stimulate B cells to produce Abs of different heavy chain classes (isotypes),Heavy chain class switching is initiated by CD40L-mediated si

7、gnals, and switching to different classes is stimulated by different cytokines.,Ig heavy chain class (isotype) switching,（蠕虫）,Ig heavy chain class (isotype) switching,Mechanisms of Ig heavy chain class switching,e. Affinity maturation in Ab responses,Affinity maturation is the process by which the a

8、ffinity of Abs produced in response to a protein Ag increases with prolonged and repeated exposure to that Ag. The increase in affinity is due to point mutations in the V regions, and particularly in the Ag-binding HVR, of the Abs produced. Affinity maturation occurs in the germinal centers of lymph

9、oid follicles.,Affinity maturation in antibody responses somatic mutation,Control of Affinity - smaller peak response (lower Ab titer); - remaining in the serum at detectable levels for much shorter periods; - lower average affinity; - usually IgM;,4. General features of Ab responses in vivo,(The immune response followed by secondary antigenic challenge) - shorter latent phase; - bigger peak response (higher Ab titer); - remaining in the serum at detectable lev