BLG 307 Lecture Notes - Clonal Deletion, Cd19, Germinal Center

34 views2 pages
28 Jan 2013
Department
Course
Professor

For unlimited access to Class Notes, a Class+ subscription is required.

Outline of Lecture 04
Immunoglobulins III, B Cell Development
I. Overview
B Cell development has two phases (see Fig. 1, p. 59):
- Antigen independent: (bone marrow), V(D)J and allelic exclusion
- Antigen dependent: (elsewhere), clonal selection, class switching,
hypermutation
II. Antigen-Independent development of B Cells
A. Occurs in the bone marrow:
1) DJ rearrangement at both heavy chain alleles (now called pro-B cell)
2) VDJ rearrangement and heavy chain expression (now pre-B cell)
3) VJ rearrangement of κ chain
4) If unsuccessful at both loci, VJ rearrangement of λ chain
5) Expression of surface IgM (now immature B cell)
6) Tolerance testing and receptor editing if anti-self
7) Migration to secondary lymphoid organs (now peripheral B cell)
B. Allelic exclusion prevents expression of other Ig loci
1) Accessibility hypothesis
txn of unrearranged gene stimulates rearrangement
txn access affects whether rearrangement occurs
2) Heavy chain regulation
block apoptosis and allow proliferation
Stop VDJ rearrangement
Start VJ κ rearrangement
Pro-B to Pre-B also has loss of CD43 marker
3) Pre-B cell receptor complex
VpreB and λ5 are surrogate light chains, help heavy chains fold
Required to progress to Pre-B cell, otherwise apoptosis
C. Two types of B cells
CD5+ in body fluids, sIgM and CD19+, secrete lots of IgM, anti-self
CD5- circulating B cells (the usual)
III. Antigen-dependent development of B cells
A. B cell activation and differentiation
1) T cell independent: relies on crosslinking of sIgM on B cells
2) T cell dependent:
T helper cell and B cell interact to activate B cell
Various T-B signals (gp39/CD40, TCR/MHCII, interleukins)
- Activated B cells differentiate into memory and plasma (Ab secreting)
cells
B. Class Switching
Occurs in germinal center
Directed by interleukins secreted by T cells (e.g. IL-4 gives IgG1 and IgE)
Upstream “switch region transcripts” are necessary
C. Affinity Maturation
The result of somatic hypermutation and selection
Occurs in germinal center also
D. Immunologic Memory
Unlock document

This preview shows half of the first page of the document.
Unlock all 2 pages and 3 million more documents.

Already have an account? Log in

Get access

Grade+
$10 USD/m
Billed $120 USD annually
Homework Help
Class Notes
Textbook Notes
40 Verified Answers
Study Guides
1 Booster Class
Class+
$8 USD/m
Billed $96 USD annually
Homework Help
Class Notes
Textbook Notes
30 Verified Answers
Study Guides
1 Booster Class