PMI 126 - Lecture 9

PMI 126 - Lecture 9 - PMI 126 Lecture 9 Possible...

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PMI 126 - Lecture 9 Possible combinatorial associations of heavy and light chains is about ~10^6 => just by different combination of V,D,J. => billion of B cells being made in bone marrow => generate receptors for almost everything. Ig DIVERSITY • Combinatorial V-(D)-J joining – Recombinase (RAG-1 and RAG-2) <= defect on one of these gene = cannot generate T/B cells • Junctional flexibility P-region nucleotide addition (P-addition) • N-region nucleotide addition (N-addition) – added by Terminal deoxynucleotidyl transferase ( TdT ), only found in developing T/B cells – before D/J join or DV join, TdT add random nucleotides in between – odd number of addition (1 or 2 nucleotides) ends up with early termination codon = dysfunctional gene. = lymphocyte dies by apoptosis • Combinatorial association of light and heavy chains • Somatic hypermutation – Activation induced cytidine deaminase ( AID ) – once a B lymphocyte has both rearranged heavy and light chains gene (B cells with IgM on the surface), and has the primary RNA, it's going to undergo RNA splicing. => single B cells make two different classes of antibodies (IgM and IgD) with the same specificity => results a newly made B cell with both IgM and IgD with only one specificity => it's a mature B lymphocyte now => mature B cell can enter the proliferatory - if it can leave the blood, it would go to organized lymphoid tissue ** only way lymphocyte gets out of blood is by binding to the specialized VEC that in the organized lymphoid tissue in the lymph node or spleen. ** NEVER FIND A B CELL WITH MORE THAN ON SPECIFICITY => B cells bind to antigen before it has IgM and IgD on the surface = signal to apoptosis => Naive Lymphocyte only last about a week = undergoes apoptosis with antigen recognition Tissue insult -> dendritic cells process the antigen -> dendritic cells carry the processed antigen to the lymph node and represent to both B cells and T cells Naive B cells bind to the antigen on the dendritic cells in the lymph node => signal transduction activates the B cell => B cells move to specialized structure in the cortex of lymph node with the active T helper cell.
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* together they form follicles (accumulation of rapidly dividing lymphocytes, mostly B cells and few helper T cells.) With T cells help (T cell also has to see the same pathogen) => only way to see it through MHC molecule presenting the processed antigen. => with T cells help, as B cells proliferate in response to the bound antigen, ends up s omatic hypermutation. * tremendous amount of mutation at the variable region genes of proliferating B cells.
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