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4/30/18The Development of B lymphocytes: Chap. 4 and ment:"Today’s"subjectsStages of BCR development: Phase I Phase"I:"Productive"vs."non gments" Phase"II"&"III":"Tolerance"induction"( "no"self"reactivity)! Receptor"editing! Clonal"deletion1
ss&Quality(check(pre/B(cell(receptor &you&generate&an&out8of8the8frame&sequence ional&Ig Most&loses&are&during&heavy&chain&development Light&chain:&more&trials!& (Pre and(λ5( IgB shuts(down(further(rearrangement(Pre B&cell&to&Immature&B&cell eavy*chain that*resists*gene*rearrangement2
Checkpoints during B cell development in bonemarrow e.&with&identical&VDJ) l&followed&by&lambda uccess&rate&then&with&additional&D ecombine&with&downstream&J pa&locus&on&other&chromosome& If&kappa&fails,&then&lambda&locus&rearranges developmentStages'in'development'B'cells'BMSLN3
s) ls Potential&multivalent &glycolipids&on&cells& tion reactive&(up&to&75%)&need&to&dealt&with:! clonal&depletion! olerance Monovalent&antigens&are&usually&soluble&proteins B&cell&becomes&non:responsive:!Expresses&IgD but&hardly&any&IgM!Half:life:&1:5&daysNemazee, D, Nat Rev Imm. 20154
4/30/18Maturing)B)cellsMaturing)B)cells enter&a&secondary&lymph&node& ve&selection)Mature'B'cellsEncountering antigen initiates many pathways They'express'both'IgM'and'IgD rgans he'follicles'for'16'hours5
4/30/18Heavy&chain&isotypes nity'antibody'secreted'in'form'of'pentameric for'low'affinity'of'binding'unit er'degree'of'avidity'needed:'isotype switch'from'IgM (pentamer)'to'other'types'(IgG,'IgA or'IgE;'bivalent)Isotype(switching Isotype n/isotype (no/change/in/epitope recognition) Isotype light/chain/not/changed /activation?induced/cytidine deaminase (AID) way's)immunobiology)Isotype)switching th,cellular,receptor), opsonization /,activation,complement,system,leading,to,lysis pathogen,and,ingestion,by,phagocytes activation,NK,cells,by,binding,to,Fc,receptors, activation,mast,cells,by,interaction,with,IgE receptor,(discussed,in,Chapter,9)6
y'somatic'hypermutations IgM has(low(affinity(binding atic(hypermutation ing(CDR(loops()(are(selected((below) rasites,)microbes)and)viruses)outside)the)body) transport)across)placenta)to)supply)fetus with)protective)antibodies diffusion)in)extravascular y'MaturationMovie&by&Jullian&Kirk&Elleker7
4/30/18Various(B(cell(tumors(reflect( s (oncogenes (controling cell(growth,(division(and(differentiation) B(cell(tumors cell( Tumors mph(nodes( (follicular(center cell(lymphoma Tumors derived(from(plasma(cells(grow(in(bone(marrow(( (myeloma((8
4/30/18 2 Heavy&chain&rearrangement&inefficient&process& In&every&Ig&rearrangement&there& is&2/3&chance&that&you&generate& an&out8of8the8frame&sequence
