October 16th/23rd , 2012- Chapter 8 -There are parts of B cell development that have no interaction with antigens and

parts that do. B-cell development in bone marrowMake receptors in bone marrowscramble them Negative selection-get rid of the self-responsive ones Development happens in response to bone marrow stromal cells Plasma cells-pour out antibody Memory cells-hang around for secondary response

Alloreactivity Negative selection happens for both B and T cells During development, your B and T cells never see foreign MHC molecule, so they could attack the many MHC molecules on the foreign transplant.

Hematopoietic stem cells in bone marrowthen at some potent become committed to become multipotent progenitor and is no longer self-renewing.

Chemokines cxcl receptor cxc r.ligand does not match up woth nomenclature with receptor.CXCL12 keeps progenitor cells in bone marrow.

Early pro-b cell is when you just begin to rearrange genes on heavy chain DJ Late pro-b ..when you finish h chain development .VDJ Pre-b cell..first one to express surface receptor that looks like bcrnotyou dont have light chain receptor yet. You make a sort of phony light chain the signal from the phony chain drives rearrangement of light chain. There isnt a ligand used to drive thisAt the end of this process it loses its adhesion ..

Not surprisingly genes are involved figure 7.4 not on exam Only when you get a signal from a functional heavy chain associated with a phony light chain does light chain start rearranging. Various proteins jump into action at various stages ..knock outs of BP1 look pretty normal. Not surprisingly proteins

How come there are no surface receptors in small pre-b There is nothing to display How do you test to see I you have a good heavy chain Make phony light chain =, which associate non covalently with heavy chain -phony light chain made up of VpreB and lambda 5 What keeps a B cell from ..more than one BCR AllELIC Exclusionif you express a particular heavy chain it will send a signal and stop heavy chain rearrangement

B cells express only one H chain and one L chain for the most partbunny experimenteven if they have DNA to code for more than one. Allotypes of immunoglobulin. There are different types of mu chains for example If we took sarahs serum and isolated a whole bunch of IgM and shot it into sarah, sarah will make antibody against it because there are allotypes of IgM (antibody would be against c region not enough variable). Once you have signal from pre-b receptorstarts to proliferate.sometimes h chains fail due to frameshift etcso once you get a good h chain it starts proliferating to make lots of daughter cells that have the same h chain and then rearranges different h chains from this. If light chain rearrangement doesnt work out the first time you can try again because it has more vs and js.assuming you dont start at last one where DNA would be deleted. You can try several times on each chromosome to make a light chain . You have two kappas and two lambdas one on each chromosome. You try kappa before lambda. A little over time you succeed at making a kappa light chain. 60% kappa, 40% lambda. If you look at someones serum and see a different ratio of kappa and lambda, they probably have some sort of B cell cancer.one clone has just taken off..a myeloma. You make things when you need them Why make a phony light chainbefore you make a light chian you want to make sure you have a functional heavy chain Heavy chain and light chain and kappa and lambda on different chromosomes.

How do you get rid of B cells that see self Two ways of becoming tolerant to self -Central tolerance (tolerance that happens in bone marrow while cell develop-getting rid of self-reactive ) vs peripeheral (mechanisms outside of bone marrow after development is finished to get rid of ones that escapes central mechanisms) tolerance Haplotype set of MHC genesMHC region not very big..small region inherited kind of like a generarely get any crossovers.