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

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

B Lymphocytes

Pro-B cell (B220low, CD43+) DJ and V-DJ rearrangement, Ig and Ig, losing CD43 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

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.

III. B-cell surface markers

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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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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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

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

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

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.

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

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

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

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.