Biology of the B Lymphocyte Review: .B cells can develop a vast repertoire of antigenic specificities Diversity-the ability to respond to many different antigenic determinants(epitopes)even if they have not been previously encountered Development of lymphocytes and how they are responsible for ·Specificity Memory Discrimination b/w "self"and "nonself
Biology of the B Lymphocyte ◼ Review: ◼ B cells can develop a vast repertoire of antigenic specificities ◼ Diversity – the ability to respond to many different antigenic determinants (epitopes) even if they have not been previously encountered ◼ Development of lymphocytes and how they are responsible for ◼ Specificity ◼ Memory ◼ Discrimination b/w “self” and “nonself
Sites of Early B-Cell Differentiation Synthesis of Ab was shown to require the presence of an organ called the bursa of Fabricius(chickens) Cells that developed into mature Ab forming cells were called bursa-derived or B cells B cell differentiation (humans) Liver in early fetus During fetal development and throughout the rest of life switches to bone marrow Bone marrow is the primary lymphoid organ for B-cell differentiation
Sites of Early B-Cell Differentiation ◼ Synthesis of Ab was shown to require the presence of an organ called the bursa of Fabricius (chickens) ◼ Cells that developed into mature Ab forming cells were called bursa-derived or B cells ◼ B cell differentiation (humans) ◼ Liver in early fetus ◼ During fetal development and throughout the rest of life switches to bone marrow ◼ Bone marrow is the primary lymphoid organ for B-cell differentiation
Ontogeny of the B Lymphocyte Differentiation pathway of B lymphocytes(Figure 7.1 Handout) Pro-B Cell Earliest distinguishable cell in the B cell lineage ·DH-DH rearrangement ·No Ig product ■Pre-B Cell ·VHDHJH rearrangement Synthesizes u chain Surrogate light chains-from two non-rearranging genes 5 and VpreB
Ontogeny of the B Lymphocyte ◼ Differentiation pathway of B lymphocytes (Figure 7.1 Handout) ◼ Pro-B Cell ◼ Earliest distinguishable cell in the B cell lineage ◼ DH-DH rearrangement ◼ No Ig product ◼ Pre-B Cell ◼ VHDHJH rearrangement ◼ Synthesizes m chain ◼ Surrogate light chains – from two non-rearranging genes l5 and VpreB
B Cell Receptor (BCR) ■Pre-BCR Iga(CD79a)and IgB(CD 79b) Associated with Ig molecules on all cells of the B cell lineage Do not bind Ag Signal transduction-transmit signal into cell after binding of Ag to the v regions of Ig H and L chains Surrogate light chains +u chain B-Cell Receptor ,H chain of the BCR may be p,δ，Y,,ore
B Cell Receptor (BCR) ◼ Pre –BCR ◼ Iga (CD79a) and Igb (CD 79b) ◼ Associated with Ig molecules on all cells of the B cell lineage ◼ Do not bind Ag ◼ Signal transduction – transmit signal into cell after binding of Ag to the V regions of Ig H and L chains ◼ Surrogate light chains + m chain ◼ B-Cell Receptor ◼ H chain of the BCR may be m, d, g, a, or e
B Cell Ontogeny Cells that do not express pre-BCR die by apoptosis Cells expressing pre-BCR undergo "positive selection" Signals via the pre-BCR induce cells to proliferate Surrogate light chain synthesis is shut down Light chain rearrangement starts Further H chain rearrangement is stopped Immature B Cells Light chains pair with m chains(membrane-bound monomeric form) Immature B cells can recognize and respond to foreign Ag, but this interaction results in long-lasting inactivation rather than expansion and differentiation
B Cell Ontogeny ◼ Cells that do not express pre-BCR die by apoptosis ◼ Cells expressing pre-BCR undergo “positive selection” ◼ Signals via the pre-BCR induce cells to proliferate ◼ Surrogate light chain synthesis is shut down ◼ Light chain rearrangement starts ◼ Further H chain rearrangement is stopped ◼ Immature B Cells ◼ Light chains pair with m chains (membrane-bound monomeric form) ◼ Immature B cells can recognize and respond to foreign Ag, but this interaction results in long-lasting inactivation rather than expansion and differentiation