15 research outputs found
Surrogate Light Chain Expression Is Required to Establish Immunoglobulin Heavy Chain Allelic Exclusion during Early B Cell Development
AbstractAllelic exclusion at the IgH locus was examined in B lineage cells of wild-type mice and mice unable to express the surrogate light chain molecule λ5 using a single-cell PCR approach. By analyzing B precursor cells containing two VHDHJH rearrangements, we found that in wild-type animals, cells are allelically excluded as soon as ÎŒ chains are expressed. Furthermore, we provide evidence that in cells expressing DÎŒ proteins VHâDHJH rearrangement is inhibited. In contrast, in the absence of λ5 protein, B precursor cells were allelically âincluded,â indicating that allelic exclusion at the IgH locus requires expression of the pre-B cell receptor either containing a ÎŒ chain or a DÎŒ chain. However, although ÎŒ chain double-producing B precursor cells are generated in λ5-deficient mice, such cells were not detected among surface immunoglobulin positive B cells
Rearrangement and Expression of Immunoglobulin Light Chain Genes Can Precede Heavy Chain Expression during Normal B Cell Development in Mice
In mouse mutants incapable of expressing ÎŒ chains, VÎșJÎș joints are detected in the CD43+ B cell progenitors. In agreement with these earlier results, we show by a molecular single cell analysis that 4â7% of CD43+ B cell progenitors in wild-type mice rearrange immunoglobulin (Ig)Îș genes before the assembly of a productive VHDHJH joint. Thus, ÎŒ chain expression is not a prerequisite to IgÎș light chain gene rearrangements in normal development. Overall, âŒ15% of the total CD43+ B cell progenitor population carry IgÎș gene rearrangements in wild-type mice. Together with the results obtained in the mouse mutants, these data fit a model in which CD43+ progenitors rearrange IgH and IgÎș loci independently, with a seven times higher frequency in the former. In addition, we show that in B cell progenitors VÎșJÎș joining rapidly initiates Îș chain expression, irrespective of the presence of a ÎŒ chain
Rearrangement and Expression of Immunoglobulin Light Chain Genes Can Precede Heavy Chain Expression during Normal B Cell Development in Mice
Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development
Differential subunit composition of the G proteinâactivated inward-rectifier potassium channel during cardiac development
Parasympathetic slowing of the heart rate is predominantly mediated by acetylcholine-dependent activation of the G proteinâgated potassium (K(+)) channel (I(K,ACh)). This channel is composed of 2 inward-rectifier K(+) (Kir) channel subunits, Kir3.1 and Kir3.4, that display distinct functional properties. Here we show that subunit composition of I(K,ACh) changes during embryonic development. At early stages, I(K,ACh) is primarily formed by Kir3.1, while in late embryonic and adult cells, Kir3.4 is the predominant subunit. This change in subunit composition results in reduced rectification of I(K,ACh), allowing for marked K(+) currents over the whole physiological voltage range. As a consequence, I(K,ACh) is able to generate the membrane hyperpolarization that underlies the strong negative chronotropy occurring in late- but not early-stage atrial cardiomyocytes upon application of muscarinic agonists. Both strong negative chronotropy and membrane hyperpolarization can be induced in early-stage cardiomyocytes by viral overexpression of the mildly rectifying Kir3.4 subunit. Thus, a switch in subunit composition is used to adopt I(K,ACh) to its functional role in adult cardiomyocytes