Antibody Production T Cells Not Required for CSR

B cells can be stimulated to undergo a DNA event called class switch recombination (CSR), which allows a B cell to change the constant heavy chain tail of the antibodies it is producing. The antibody isotype [immunoglobulin M (IgM), IgG, IgE, or IgA] is defined by this tail, which binds to receptors on the target cells to initiate different cellular responses to the same anitgen. Litinskiy et al. describe a mechanism for CSR that does not require T cell-B cell interaction. Cultured B cells stimulated with exogenous BLyS or APRIL underwent CSR, as detected by small amounts of switch circle DNA, an extrachromosomal product of CSR, and the expression of transcripts from this event. The addition of BLyS or APRIL with interleukin (IL)-10, IL-4, or tranforming growth factor-β (TGF-β) potentiated CSR. BLyS and APRIL both stimulated the activity of the transcription factor NF-B. BLyS or APRIL stimulated increased IgA and IgG antibody secretion. The authors determined that interferons, CD40 ligand, and bacterial lipopolysaccharide stimulated BLyS and APRIL production in dendritic cells or monocytes, which promoted CSR in B cells. CSR in response to activated dendritic cells was blocked by treatments that neutralized BLyS or APRIL action. When the B cell receptor was activated and the cells were exposed to activated antigen-presenting cells, then IgA and IgG were secreted through a process that required BLyS and APRIL. Thus, antigen-presenting cells alone may be able to control B cell antibody production without requiring a T cell intermediary. MacPherson and Lamarre discuss the relevance of these results for autoimmune disease.

A. J. Macpherson, A. Lamarre, BLySsful interactions between DCs and B cells. Nat. Immunol. 3, 798-800 (2002). [Online Journal]

M. B. Litinskiy, B. Nardelli, D. M. Hilbert, B. He, A. Schaffer, P. Casali, A. Cerutti, DCs induce CD40-independent immunoglobulin class switching through BLys and APRIL. Nat. Immunol. 3, 822-829 (2002). [Online Journal]