Here are the major developmental stages of B cell development:
- Stem Cell Hematopoietic stem cells in the bone marrow give rise to the B cell lineage.
- Pro-B Cell The earliest committed B cell precursor stage. V(D)J recombination of the immunoglobulin heavy chain locus begins, generating the mu heavy chain.
- Pre-B Cell Successful mu heavy chain rearrangement allows progression to this stage. The pre-BCR complex (mu + surrogate light chains) is expressed and tested for autoreactivity. V(D)J recombination of the light chain locus occurs.
- Immature B Cell Cells that produce a functional, non-autoreactive BCR (mu + light chain) can exit to the periphery as immature B cells. Further selection against autoreactive BCRs occurs.
- Transitional B Cell Immature B cells transitioning to mature naive B cells in the spleen. Further tolerance checkpoints remove remaining autoreactive clones.
- Naive Mature B Cell Non-autoreactive B cells become mature naive B cells co-expressing IgM and IgD BCRs. They circulate awaiting antigen activation.
- Activated B Cell Upon antigen binding and T cell help, mature B cells become activated and migrate to germinal centers.
- Germinal Center B Cell Activated B cells undergo somatic hypermutation of BCR genes to increase affinity. Class switch recombination allows isotype switching.
- Memory B Cell Some activated cells differentiate into long-lived memory B cells.
- Plasma Cell Other activated B cells terminally differentiate into antibody-secreting plasma cells with a switched isotype (IgG, IgA, IgE).
This multistage process allows extremely diverse BCR specificities while enforcing central and peripheral tolerance to avoid autoreactive B cell clones. Further details about B cell development will be revealed in later sections of this textbook.
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Source: Claude 3 Sonnet response prompted and edited by Joel Graff.
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