Switch recombination in normal IgA1+ Blymphocytes.

Abstract

Most B lymphocytes in normal individuals express two classes of cell-surface immunoglobulins, IgM and IgD. The specificity of the two antigen receptors is identical since they are produced by transcription and differential splicing of the same variable region gene segment to the heavy-chain constant region gene segments for both ,u and 8 heavy chains. B lymphocytes expressing other immunoglobulin isotypes, IgG, IgA, or IgE, are rare and not well characterized. Particularly controversial is the molecular mechanism of their isotype switch. Here we use high-gradient magnetic cell sorting and fluorescence-activated cell sorting to purify surface IgAlbearing B lymphocytes from human blood for cellular and molecular analysis. These cells express no immunoglobulin class other than IgAl and are a relatively uniform population with regard to expression of other cell-surface molecules. They are resting cells in terms of cell cycle and activation marker analysis. The molecular basis for class switching in the IgAl1 cells is not differential transcription or splicing. Rather, switch recombination involving deletion of DNA has occurred on both immunoglobulin heavy-chain gene loci, including the allefically excluded one, and appears to have been directed to IgAl under normal physiological conditions.

Premature replacement of μ with α immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation

“…Interestingly, normal mIgA+ cells purified from human blood include a high proportion of cells expressing CD38, a marker shared by immature cells and cells engaged to plasma cell differentiation (31). Whereas the IgA BCR has been shown to be subjected to CD22 inhibition as for IgM (32), other aspects may differ in signals provided both by classes of BCR and by impact on the behavior of B cells during primary or secondary responses to antigens.…”

Memory B lymphocytes migrate to bone marrow in humans

“…Ϫ IgM ϩ bone marrow cells thus resemble germinal center B cells although their phenotypic profile does not match precisely with that of any of the germinal center B-cell subpopulations (20,26,27) or that of memory B cells in the circulation (28). The phenotypic profile thus suggests that this bone marrow B-cell population includes a mixture of more or less recent B-cell immigrants of germinal center origin that may have undergone phenotypic modification before or after entry into the bone marrow.…”

Mechanisms of chromosomal translocations in B cell lymphomas

“…The excised DNA is circularised to a switch circle and later lost from the cell joined, such that a new C H gene is placed downstream of the V region exon (Figure 2b). Although B cells carry only one functional V H gene rearrangement, class switching often takes place on both IgH alleles (Irsch et al, 1994). The putative`class switch recombinase' is still unknown, but the DNA ± PK complex, which is involved in V(D)J recombination and non-homologous double-strand DNA break repair (see above) is also needed for class switch recombination (Maizels, 1999).…”