1. Jianzhong Chen, Ph. D. Institute of Immunology, ZJU
B lymphocytes
Jianzhong Chen, Ph. D.
Institute of Immunology, ZJU

3. I. B cell ontogeny
Development：in mammals, B lymphocytes develop and mature in bone marrow; in birds, they have a specialized site of B-cell generation--- the bursa of Fabricius.
About 5-15％ of the circulating lymphoid pool are B cells.
There are two stages
Ag-independent stage---BM
Ag-dependent stage---peripheral

4. B Lymphocytes

5. Pro-B cell (B220low, CD43+) DJ and V-DJ rearrangement, Ig and Ig,
losing CD Pre-B cell (expression of surrogate BCR)
L chain V-J rearrangement immature B cell (mIgM+)
negative selection mature B cell (mIgM+ and mIgD+)
(naïve B cell)
Ag, positive selection AFC/long lasting memory B cell
Negative selection Positive selection
clonal deletion follicular dendritic cell
clonal anergy

7. II. Distribution of B cells
Blood, lymphoid organs (lymph node, spleen, tonsil etc.) and mucosa.
Naive mature B cells exit the bone marrow and migrate into the periphery. If these mature B cells encounter specific antigen, they become activated or tolerized.
Following activation, Ag-specific B cells differentiate into antibody-forming cells (AFC) or memory B cells in the germinal centre.

8. III. B-cell surface markers

9. 1. BCR complex BCR (mIg)：VH,VL----Ag mature B cells: mIgM and mIgD.
Function: specifically recognizes antigen.
Ig/Ig (CD79a/CD79b): heterodimer cytoplasmic domains contain ITAM.
Function: 1. transfers the signals that
lead to B cell activation.
2. transports the Ig

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11. 2. Co-receptors CD19/CD21/CD81complex CD21=CR2, C3dR, EB virus R
CD19/CD21/CD81 interactions with complement associated with antigen play a role in antigen-induced B-cell activation.

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13. 3. Co-stimulatory molecules
(1)CD40 interacts with CD40L (Th cell)
(2)CD80(B7.1), CD86(B7.2)
expressed on activated B cells
(3)ICAM-1, LFA-1

14. 4. Mitogen receptors
LPS-R, PWM-R
5. Other receptors
CD20
CD22
CD32

15. CDs related to B cell activation
BCR complex
co-receptor
CDs related to B cell activation

16. IV. B-cell subsets
B1 cells (CD5+): Many of the first B cells that appear during ontogeny express CD5, a marker originally found on T cells. (express mIgM, no mIgD). They respond well to TI-Ag and may also be involved in the Ag processing and presentation to T cells.
Functions
1. produce anti-bacterial IgM the first line of defense against microorganisms;
2. produce polyreactive Ab clearance of denatured self components;
3. produce auto-Ab, thereby participating in the pathogenesis of some autoimmune diseases.

17. The mechanism of TI-Ag activating B1 cells
（A）： TI-1 Ag
（B）： TI-2 Ag

18. B2 cell : CD5- B cells.
mIg: IgM, IgD
after antigenic stimulation, in
the presence of Th, they
produce more IgG than IgM

19. differences between B-1 and B-2 cells
characteristics
B-1 B cell
B-2 B cell
development period
foetal period
postnatal
Renew style
self-renewal
input of bone marrow precursor cells
Spontaneous Ig
high
low
specificity
Ig isotype
Mainly IgM
Mainly IgG
somatic mutation frequency
Low or no
T-independent response
yes
possible
T-dependent response

20. V. Functions of B cells 1. Production of antibody
Abs prevent microorganism entry into cells and eliminate microorganisms by opsonization causing phagocytosis, complement activation and toxin neutralization.
2. Ag presentation to T cells
3. Immune regulation
Secretion of cytokines (TNF, IFN,IL-12) →M, DC, NK, B cell.
Co-stimulation of T cells→T cell proliferation.