Δευτέρα 25 Απριλίου 2016

LPS stimulates IgM production in vivo without help from non-B cells

Gram-negative bacterial LPS induce murine B-cell activation and innate (polyclonal) Ab production. Mouse B cells express the LPS signaling receptor (TLR4), yet how LPS activates B-cell responses in vivo is not known. Can LPS directly stimulate B cells to induce innate Ab production? Is activation of non-B cells also required? To address these questions, we transfused LPS-responsive (Tlr4+/+) or non-responsive (Tlr4–/–) B cells into LPS-responsive or non-responsive mice. Increased expression of the early activation markers CD69 and CD86 could be induced on transfused Tlr4–/– B cells by injecting LPS subcutaneously into Tlr4+/+ mice, demonstrating indirect activation of B cells by TLR4-responsive non-B cells in vivo, but the Tlr4/ B cells did not increase serum IgM levels. In contrast, when Tlr4–/– recipients were transfused with Tlr4+/+ B cells, LPS induced large amounts of serum IgM and LPS could also enhance specific Ab production to a protein that was co-injected with it (adjuvant response). Thus, LPS-exposed non-B cells mediated increased surface expression of early B-cell activation markers, but this response did not predict innate Ab responses or LPS adjuvanticity in vivo. Direct stimulation of B cells by LPS via TLR4 was necessary and sufficient to induce B cells to produce Ab in vivo.



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