IgD class switch recombination is not controlled through the immunoglobulin heavy chain 3′ regulatory region super-enhancer

In secondary lymphoid organs,mature B cells express membrane immunoglobulin(Ig)of M and D isotypes(IgM and IgD,respectively)of the same specificity through alternative splicing of a pre-mRNA encompassing the VDJ variable region and Cμand Cδheavy chain constant exons.1 After encountering antigen,B cells undergo class switch recombination(CSR)by which the Cμgene is substituted with Cγ,Cεor Cα,thereby generating IgG,IgE and IgA antibodies of the same antigenic specificity but with new effector functions.CSR requires the DNA-editing enzyme activation-induced deaminase(AID).

SNAP23-Kif5 complex controls mGlu1 receptor trafficking

Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.

Retraction Note:3′RR and 5′Eμimmunoglobulin heavy chain enhancers are independent engines of locus remodeling

The authors have retracted this Correspondence.After the publication of this correspondence,it came to the authors’attention that the control RAG2^(−/−)mouse was a RAG2^(−/−)γc^(−/−)mouse.This point resulted in the conclusions being considered invalid.The authors apologize to the journal and its readers for any inconvenience caused.

Retraction Note:Trans-silencing effect of the 3′RR immunoglobulin heavy chain enhancer on Igκtranscription at the pro-B cell stage

The authors have retracted this Correspondence.After the publication of this correspondence,it came to the authors’attention that the control RAG2^(−/−)mouse was a RAG2^(−/−)γc^(−/−)mouse.This point resulted in the conclusions being considered invalid.The authors apologize to the journal and its readers for any inconvenience caused.

Trans-silencing effect of the 3′RR immunoglobulin heavy chain enhancer on Igκtranscription at the pro-B cell stage

Due to their impact on nuclear organization,enhancers are master regulators of cell fate.1,2 The immunoglobulin heavy chain(IgH)locus undergoes numerous changes(such as transcription,accessibility,DNA breaks,and mutations)throughout B-cell differentiation.Several of these events are controlled by the IgH 3′regulatory region(3′RR).The 3′RR is the master control element of mature B-cell IgH transcription,3 somatic hypermutation(SHM),4,5 conventional class switch recombination(CSR),4,6–10 and locus suicide recombination(LSR).11 In contrast,the 3′RR is expected to be dispensable for V(D)J recombination.12,13 During Bcell development,the heavy and light chain loci are poised for their VDJ and VJ rearrangements,respectively.The IgH locus rearranges first,with D-J joining at the pro-B-cell stages,followed by V-DJ joining at the pre-B-cell stage.The Igk locus is poised for VJ rearrangements at the pre-B cell stage.