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Immuno B-cell Developement Lecture Notes.docx

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Health Sciences
Course Code
Jonathan Bramson

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B-Cell Development The whole process  B-Cell= in bone marrow (generates BCR)= Negative Selection= Leaves BM as immature B-cells  In periphery= becomes activated= mature B-cell (effector B-cells)  Either becomes plasma cell or memory B-Cell Bone Marrow  Everything starts as multipoitent progenitor cells o Either become common lymphoid progenitor (gives rise to B cell) or common myeloid o Remember Common lymphoid progenitorpro-B-cell mature B-cell  Stomal cells=non-lymphoid= form adhesive contacts with the B-cell o Source of cytokines/chemokines involved with B-cell differentiation B-cell maturation (we only talk about B-2 cells in lecture)  Start off with early pro-B-cell  Becomes late B-cell gives large pre-B-cellsmall pre-B-cell immature B-Cell matures  Note: Heavy chain rearrangement always occurs first (Always start with DJ)  Have x2 alleles= two recombination events  DJ arranges first on heavy chain and the V to DJ occurs when this occurs it forms the heavy chain (mu heavy chain)  If successful= get mu chain expressed as pre-B-cell receptor o Need to be expressed along with a surrogate light chain (lambda 5 or VpreB) o Note the surrogates DO NOT need to o Triggers light chain rearrangement o If you cannot recombine the heavy chain= go to next chromosome o If you cannot recombine here= die  Crosslinking of pre-BCR= stops heavy chain rearrangement + proliferation  Get resting pre-B-cell (still has heavy and surrogate light chain)  Light chain rearrangement o Have two loci on each chromosome (i.e. four opportunities) o Have kappa chain (rearrangement occurs here first on one chromosome= if fails= goes to second kappa on other chromosome) o If this fails= go to the second loci= lambda loci (rearrangement occurs here first on one chromosome= if fails= goes to second lambda on other chromosome) o If none work= die o If all successful= get IgM expression and you become an immature B-cell  Note: even though all cells will have same heavy chain, the light chain recombination events= creates diversity  MARKER OF MATURATION= high levels of IgD and low levels of IgM Allelic Exclusion  Igh a/a and Igh b/b (mom and dad both have different allotypes)  Allotype= polymorphisms in the constant region)!  F1= has B-cells that are either expressing isotype a or isotype b… NOT both!!!  Even though the F1 is Igh a/b  This is occurring in the constant region not the variable region Isotypic Exclusion  Only will have one light chain expressed per cell Negative selection in B-cells  Occurs in the bone marrow  Test for self reactivity= if too strong reaction= central tolerance (because it occurs in central lymphoid tissue)  Fate of self reactive B-cells o Cell death (cell dies via apoptosis) o Receptor editing (occurs before cell death= frantically re-arrangeing other light chains)  Self antigen triggers crosslinking= get RAG expression= can continue light chain rearrangement= B-cell continues normal development  Failing editing= undergo apoptosis o Anergy (this cell can no longer be activated even with T-cell help= get less IgM on surface= get defective signally= no responsiveness= eventually
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