Stages of B Lymphocyte Development

During their maturation, cells of the B lymphocyte lineage go through distinguishable stages, each characterized by distinct cell surface markers and a specific pattern of Ig gene expression (Fig. 8-14). The major stages and the events in each are described next.

The Pro-B and Pre-B Stages of B Cell Development

The earliest bone marrow cell committed to the B cell lineage is called a pro-B cell. Pro-B cells do not produce

Ig, but they can be distinguished from other immature cells by the expression of B lineage-restricted surface molecules such as CD19 and CD10. Rag proteins are first expressed at this stage, and the first recombination of Ig genes occurs at the heavy chain locus. This recombination brings together one D and one J gene segment, with deletion of the intervening DNA (Fig. 8-15A). The D segments that are 5' of the rearranged D segment and the J segments that are 3' of the rearranged J segment are not affected by this recombination (e.g., D1 and J2 to J6 in Fig. 8-15A). After the D-J recombination event, one of the many 5' V genes is joined to the DJ unit, giving rise to a rearranged VDJ exon. At this stage, all V and D segments between the rearranged V and D genes are also deleted. V-to-DJ recombination at the Ig H chain locus occurs only in committed B lymphocyte precursors and is a critical event in Ig expression because only the rearranged V gene is subsequently transcribed. The TdT enzyme, which catalyzes the nontemplated addition of junctional N nucleotides, is expressed most abundantly during the pro-B stage when VDJ recombination occurs at the Ig H locus and levels of TdT decrease before light chain gene V-J recombination is complete. Therefore, junctional diversity attributed to addition of N nucleotides is more prominent in rearranged heavy chain genes than in light chain genes. The heavy chain C region exons remain separated from the VDJ complex by DNA containing the distal J segments and the J-C

Stage of maturation

Stem cell

Pro-B

Pre-B

Immature B

Mature B

Proliferation

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