After production in the BM, immature surface IgM+ B cells migrate to the spleen where they differentiate through distinct transitional B cell stages termed T1 and T2, before differentiating into long-lived mature follicular (FO) or marginal zone (MZ) B cells. In a bid to prevent autoreactivity, immature B cells which encounter Ag capable of cross-linking their newly expressed BCRs are eliminated by a variety of mechanisms. Quiescent small pre-B cells then undergo V-J rearrangement of the Ig light chain, allowing the production of a complete functional BCR with a unique specificity that is expressed as IgM on the surface of immature B cells. Signalling through the pre-BCR drives intense proliferation and differentiation into the small pre-B cell stage. The recombined heavy chain then associates with the surrogate light chains and the Ig/ dimer to form the pre-B cell receptor (pre-BCR) which is expressed on the cell surface. This is followed by V-DJ recombination yielding a functional heavy chain protein (Ig) in large pre-B cells. During B cell development, rearrangement of the Ig heavy chain occurs first, commencing with D-J recombination, which takes place in the common lymphoid progenitors (CLPs) and pre-pro B cells. Immunoglobulins consist of two identical heavy and light chains, which are joined by disulphide bonds. B-cell development and B-cell subsets (Rebecca Newman)
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