University:
York University
Course:
SC/BIOL 3120 | Immunobiology
Academic year:

2023
Views:

391

Pages:

3
Author:

Niklas

Lymphocyte Development B-Cell Development Clonal Selection Theory and Generation of Diversity: individual B and T-cell receptors are randomly generated by gene segment rearrangements and each have an individual specificity each cell has many coples of the same receptor surface that binds to a single cell type Generation of Deletion Clonalslection and pansion when a Bor T-cell interacts with its specific (cagnate) antigen, it is "selected" and activated activation results in proliferation, producing a large number of clones Antiess C →each clone is reactive against the antigen that initially stimulated the original lymphocyte Lymphoid Cell Development: Primay lymphadagas Ceast thring the body Bone Marrow The Site of Hematopoiesis: B-cell (like T-cell) development begins in the bone marrow (HSPCLP) and is complemented in the periphery Hematopoietic stages are defined by cell surface markers, transcription factor expression, and Ig gene rearrangements Stem cells within the bone marrow differentiate into many cell types. -Stromal cells in bone marrow provide support and growth factors to developing cells Stages of B-cell development in bone marrow: Hematopoietic Stem Cell (HSC) Common Lymphoid Pre cursor (CLP) Pro B-cell (Pro-B) VDJ recombination in heavy chain Pre B-cell (Pre-B) Heavy chain expression VJ recombination in light chain Immature B-cell (Immature B) Leaves bone marrow and goes into periphery, where it will become naive IgM expression Negative selection VDJ Recombination: (Pro-B) occurs in heavy chain very random non-productive rearrangement: bad stuff produced that we do not need addition of random nucleotides can disrupt the reading frame productive rearrangement: good stuff produced that we need 2 chances to become productive (mom & dad) surrogate light chain: holds the place of the light chain have no signaling/binding capacity allows us to see if the heavy chain is functional Vpre B and λ5 Pre-BCR: made up of μ heavy chain plus the surrogate light chain, inhibiting rearrangement of λ allele #2 and induces κ rearrangement ↑ Pre-B no functional difference between h and λ reason for both gives us more ways to be productive kappa usually wins over lambda because its shorter mom's K- dad's mom's dad's A apoptosis (if still not productive) expression of constant regions end of pre B-cell stage Heavy-chain DNA LV LVn) D1 D14 C C26 C24 S 6.5 4.5 55 34 21 15 14 12 kb kb kb kb kb kb kb kb Close Far together apart ↓ most likely net inherited inherited together together chain DNA 5 LV1 LV2 LV(n) Recombination 23 25 kb kb A-chain DNA LV2 LV3 J2 C2 14 4 LVT 13 C3 1C1 Recombination 19 55 1.2 2.0 1.3 19 1.4 1.7 1.3 kb kb kb kb kb kb kb kb kb Heavy-chain DNA LV LVn) D1 D14 C26 Ca Splicing 65 4.5 55 34 21 15 14 12 kb kb kb kb kb kb kb kb Figure B-cells that come out of the developmental process will have MANY BCR surface antibodies have the same specificity with the same variable region (from recombination) BUT their BCR can have different isotypes due to alternative splicing.