B Cell Differentiation

1. B Cell Differentiation

2. B cells biology B cells, also known as B lymphocytes, are primarily generated from hematopoietic stem cells which play a central role in the immune-pathogenesis of glomerulonephritides and transplant rejection. There still much remains to be understood about B cell biology in order to determine the timing, duration, and context of optimal therapeutic response to B cell-targeted approaches.

3. B cells function B cells can secrete antibodies through multiple mechanisms and their antibodies are the central elements of humoral immunity which against an almost unlimited variety of pathogens. B cells contribute to disease pathogenesis by providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and progression. The antigen-recognition molecules of B cells are the immunoglobulins (Ig). These proteins are produced by B cells in a vast range of antigen specificities, each B cell producing immunoglobulin of a single specificity.

4. B cells development In the earliest B cell lineage, committed precursors ( ) Ig genes exist in a germline configuration. Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B cell lineage development. During the differentiation of pro-B cells into cells, a rearrangement in the heavy chain locus begins in early pro-B cells. pro-B cells Bone Marrow(BM) pre-B EBF1 Pro-B cell CD19+ CD10+ CD34+ IgM- Pre-B cell CD19+ CD10+ CD34- IgM- This which typically occurs at both alleles of the heavy-chain locus, at which point the cell becomes a late pro-B cell. And then a successful rearrangement means the cell progresses to become a pre-B cell.

5. B cells development Bone Marrow(BM) The chance of generating pre-B cell is less than 55%. EBF1 Pro-B cell CD19+ CD10+ CD34+ IgM- Pre-B cell CD19+ CD10+ CD34- IgM- Immature B cell CD19+ CD10+ CD34- IgM- Once these rearrangements are successfully completed, transcription begins and a mature mRNA encoding the μ heavy chain is produced, which accumulates in the cytoplasm. Next the pre-B cells become , and then develop to . Mature B cell CD19+ CD10- CD34- IgM++ immature B cells mature B cells

6. B cells differentiation Spleen Bone Marrow(BM) T1 CD21 T2 CD21 exit the bone marrow and enter the blood to complete their maturation program in secondary lymphoid tissues, preferentially in the . EBF1 Immature B cells Transitional B cell CD19+ CD10+ CD34++ CD24++ Pre-B cell CD19+ CD10+ CD34- IgM- Naive Mature B cell Immature B cell CD19+ CD10+ CD34- IgM- Pro-B cell CD19+ CD10+ CD34+ IgM- Igα, Igβ Mature B cell CD19+ CD10- CD34- IgM++ spleen Transitional cells then finalize their maturation process and give rise to . naivemature B cells

7. B cells differentiation Spleen Marginal Zone B cell CD19+ CD23+- CD21++ Bone Marrow(BM) T1 CD21 T2 CD21 EBF1 Follicular B Cell CD19+ CD23+- CD21-/+ Transitional B cell CD19+ CD10+ CD34++ CD24++ Naive Mature B cell Pre-B cell CD19+ CD10+ CD34- IgM- Immature B cell CD19+ CD10+ CD34- IgM- Pro-B cell CD19+ CD10+ CD34+ IgM- Igα, Igβ Mature B cell CD19+ CD10- CD34- IgM++ Once the immature B cells leave the bone marrow for the periphery and undergo the aforementioned transitional stages, they develop either into or into . marginal zone B cells follicular B cells

8. B cells differentiation Spleen Antibodies Marginal Zone B cell Bone Marrow(BM) T1 CD21 T2 CD21 EBF1 Follicular B Cell Plasmablast Plasma cell Transitional B cell CD19+ CD10+ CD34++ CD24++ Naive Mature B cell Pre-B cell CD19+ CD10+ CD34- IgM- Immature B cell CD19+ CD10+ CD34- IgM- Pro-B cell CD19+ CD10+ CD34+ IgM- Igα, Igβ Mature B cell CD19+ CD10- CD34- IgM++ Pre-GC B cell Germinal Center The purpose of the germinal center reaction is to enhance the later part of the primary immune response. Some differentiate first into and then into . plasma cells germinal center cells plasmablasts

9. B cells differentiation Spleen Antibodies Marginal Zone B cell Bone Marrow(BM) T1 CD21 T2 CD21 EBF1 Follicular B Cell Plasmablast Plasma cell Transitional B cell CD19+ CD10+ CD34++ CD24++ Naive Mature B cell Pre-B cell CD19+ CD10+ CD34- IgM- Immature B cell CD19+ CD10+ CD34- IgM- Pro-B cell CD19+ CD10+ CD34+ IgM- Igα, Igβ Memory B cell Mature B cell CD19+ CD10- CD34- IgM++ Pre-GC B cell Germinal Center Unswitched Switched germinal center cells memory B cells Other differentiate into  . Memory B cells are long-lived descendants of cells that were once stimulated by antigen and had proliferated in the . These cells divide very slowly if at all, and they express surface immunoglobulin, but do not secrete antibody at a high rate. germinal center

10. Plasma cells • The differentiation of a B cell into a plasma cell is accompanied by many morphological changes that reflect its commitment to the production of large amounts of secreted antibody. Plasma cells have abundant cytoplasm dominated by multiple layers of rough endoplasmic reticulum. These plasma cells will migrate to the bone marrow, where a subset of them will live for a long period of time. Plasma cells obtain signals from bone marrow stromal cells that are essential for their survival. These plasma cells provide a source of long-lasting high-affinity antibody.

11. Diseases of B cell differentiation B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells.

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