Transitional B-2 B cell
Marginal zone B-2 B cell
Marginal zone B-2 B cell
FIGURE 8-17 B lymphocyte subsets. A, Most B cells that develop from fetal liver-derived stem cells differentiate into the B-1 lineage. B, B lymphocytes that arise from bone marrow precursors after birth give rise to the B-2 lineage. Two major subsets of B lymphocytes are derived from B-2 B cell precursors. Follicular B cells are recirculating lymphocytes; marginal zone B cells are abundant in the spleen in rodents but can also be found in lymph nodes in humans.
cell receptor for self antigens contributes to whether a maturing B-2 B cell will differentiate into a follicular or a marginal zone B cell. This cell fate decision represents a positive selection event in B lymphocytes that is linked to lineage commitment.
Most mature B cells belong to the follicular B cell subset and produce IgD in addition to IgM. Each of these B cells coexpresses | and 8 heavy chains using the same VDJ exon to generate the V domain and in association with the same k or X light chain to produce two membrane receptors with the same antigen specificity. Simultaneous expression in a single B cell of the same rearranged VDJ exon on two transcripts, one including C| exons and the other C8 exons, is achieved by alternative RNA splicing
(Fig. 8-18). A long primary RNA transcript is produced containing the rearranged VDJ unit as well as the C| and C8 genes. If the primary transcript is cleaved and polyad-enylated after the | exons, introns are spliced out such that the VDJ exon is contiguous with C| exons; this results in the generation of a | mRNA. If, however, the VDJ complex is not linked to C| exons but is spliced to C8 exons, a 8 mRNA is produced. Subsequent translation results in the synthesis of a complete | or 8 heavy chain protein. Thus, selective polyadenylation and alternative splicing allow a B cell to simultaneously produce mature mRNAs and proteins of two different heavy chain isotypes. The precise mechanisms that regulate the choice of polyadenylation or splice acceptor sites by which the rearranged VDJ is joined to either C| or C8 are poorly understood, as are the signals that determine when and
Alternative processing of a primary RNA transcript results in the formation of a |i or 8 mRNA. Dashed lines indicate the H chain segments that are joined by RNA splicing.
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