B lymphocytes Jianzhong Chen, Ph D Institute of Immunology, ZJU
B lymphocytes Jianzhong Chen, Ph. D. Institute of Immunology, ZJU
Generative Peripheral ymphoid organs lymphoid organs Mature Recirculation Bone lymphocyte B lymphocytes marrow lineage stem cell Bone marrow“→pod-s[ Lymph nodes Spleen Mucosal and Thymus Blood cutaneous lymphocyte lymph Lymphoid tissues neage Mature T lymphocyt Recirculation (ElsevierAbbas&Lichtman:BasicImmunologyUpdated2e-www.studentconsult.com
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 As g- independent stage---BM Ag-dependent stage---peripheral
• 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 I. B cell ontogeny
B Lymphocytes Bone marrow Peripheral lymphoid tissue Mem Antibody Plasma cells Antiges rearrangement 2 (2 Mature Mature B cells B cells Maturation into mature Antigen-dependent proliferation antigenetically committed B cells
B Lymphocytes
Pro-B cell(B220ow. CD43*) DJ and v-DJ rearrangement, lga and lgp losing cd43 - Pre-B cell(expression ofsurrogate BCr) L chain v-j rearrangement immature B cell(mIgmt) negative selection mature B cell (mIgMt and mlgDf) (naive B cell) Ag, positive selection, FC/long lasting memory B cell Negative selection Positive selection clonaldeletion follicular dendritic cell clonal anergy
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
Delete pre-BCR BCR IgM Pre-B Immature Mature Allelic exclusion Negative selection Clonal expansion Receptor editing
I. 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 celIS(afc) or memory b cells in the germinal centre
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
I. B-cell surface markers
III. B-cell surface markers
1. BCR complex BCR(mlg): VH, VL----Ag mature B cells: mIgm and mIgd Function: specifically recognizes antigen ga/gB(CD79aCD79b ) heterodimer cytoplasmic domains contain ITAM Function: 1. transfers the signals that lead to b cell activation 2. transports the Ig
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
Microbe Cross-linking Adapter of membrane proteins Ig by antigen Tyrosine ITAM phosphorylation ⊙ ⊙ events ( BIk (BIk LynFyn PLCy GTP/GDP exchange activation on Ras. Rac Biochemical intermediates nositol trisphosphate司 increased cytosolic Ca2+Diacylglycerol ( DAG)RasGTP, RacGTP Active Ca2+-dependent enzymes PKC ERK JNK enzymes Transcription factors NFA NF-K
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