- # of genes on the human genome

25k-30k

- the generation of b-cell diversity is fundamentally composed of this

randomly attached segments of genes

D segment

- the general pattern of segments on a gene encoding for an antibody

LV(D)JC

- function resides in this segment of heavy chains

C segment

- following heavy and light chain rearrangement we describe the B cell as

antigenically committed

- the L segment if removed in the ER after this structure is formed and before we have the completed the heavy/light chains

Nascent polypeptide

- this segment combines with the J segment first in the formation of the heavy chain from the genes -->mRNA--> protein

D segment

Before processing and after translation the heavy chain contains the LVDJ and what other components?

extra J segments, Cmew and Cdelta segments, & introns

- this causes the DNA to no longer be completely totipotent

Removal of unneeded D, V, & J segments (degradation)

- Recombination signal sequences (RSS) consist of these three complementary pieces of 12 or 23 nucleotides

Heptamer (12), Spacer, Nonomer (23)

- this type of gene is utilized to help hold the RSS together in addition to the hydrogen bonds formed with the complementary bases as the loop of DNA is created prior to deletion

RAG (recombination-activating genes)

RAG-1 & RAG-2 are found only in these cells

lymphocytes

- prior to recombitance and ligation nucleotides by these two names can be added or removed at random

P (palindromic) and T (nontemplated) nucleotides

- this type of rearrangement is required to avoid apoptosis

productive

- these are created due to the creation and then cleavage of a hairpin

P (palindromic) nucleotides

- this enzyme is used to create N nucleotides and can be used as a marker enzyme for this process

terminal deoxynucleotidyl transferase (TdT)

- heavy and light chain rearrangements as well as P and N addition constitute the diversity found in this variable region of an antibody

CDR 3

- this diversity creating process occurs only in B cells and provides diversity for CDR1 and CDR2

- it occurs following exposure to antigens in the germinal centers of the lymph node

somatic mutation

-somatic hypermutation consists of these type of mutations in the CDR1 and CDR2 regions at a rate 1mil times higher than normal

Point mutation

- this enzyme is essential for carrying out the deamination of cytosine to uracil in the process of somatic hypermutation

- it is made only in proliferating B cells

- can induce somatic hypermutation when added to other proliferating cells (fibroblasts)

Activation-induced Cytidine Deaminase (AID)

- the "fine-tuning" of antibodies allows for this improvement on the antigen-specific antibodies

Tighter, quicker antigen binding

- T cells undergo all the diversifying activities that B cells do for their TcRs except this

Somatic Mutation

- occurring ONLY during an active immune response the unique V(D)J segment can bind to any of the types of C segments to create different isotypes to produce this

Class switching

- AID deaminates the cytosines between the switch regions and adds Uracil in its place. Following that addition Uracil is removed by its glycosylase, excised by an endonuclease (APE1) and in its place this is left

- helps the new ends find each other

Nicks

- the only problem with a switch comes with what characteristic following the recombinase and ligase activity

Irreversible loss of DNA

- the presence of these molecules helps to determine which isotype the antibodies will switch to

cytokines

- this cytokine induces IgG2 formation

gamma Interferon (IFN-y)

this cytokine induces production of IgG4 or IgE

IL-4

- a lack of AID would produce a greater amount of low-affinity of this antibody

IgM

Cap (5' end) & Poly-A signal

- the location of this affects whether an IgM will be transmembrane or secreted

- the location of this affects whether an IgM or IgD will be created (membrane or secreted)

Poly-A tail

- what is the Poly-A order for creating secreted and membrane-bound IgM and IgD

Secreted IgM--> Membrane IgM--> Secreted IgD--> Membrane IgM

- this process is required if secreted or membrane IgD is to be created

Splicing of IgM constant region

- rearrangement is required to activate this part of the genes with this other part of the gene due to closer proximity following splicing

Promoter <--> Enhancer

- these two drugs are mouse/human monoclonal derivatives used in clinical practice using mouse CDRs and human framework and constant regions

Rituximab (Anti CD20 agains non-Hodgkins Lymphoma)

Herceptin (Anti HER2 against breast cancer)

- the chromosome origin for kappa/lambda light chains

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