The CD40 ligand expressed by human B cells costimulates B cell responses.

Abstract

The possibility that activated B cells might express a ligand for CD40 that was of functional importance for B cell responses was examined by using highly purified human peripheral blood B cells, as well as a variety of B lymphoblastoid cell lines and hybridomas. Following stimulation with the combination of a calcium ionophore and a phorbol ester, human B cells bound a soluble fusion protein containing the extracellular portion of CD40 and the Fc region of IgG1 (CD40.Ig). A variety of B cell lines and hybridomas also bound CD40.Ig, either constitutively or after activation. In addition, CD40.Ig specifically immunoprecipitated a 33-kDa glycoprotein from surface 125I-labeled activated B cells. The nucleotide sequence of the coding region of the CD40 ligand mRNA amplified by RT-PCR from activated T cells and B cell lines was identical. The CD40 ligand expressed on human B cells was important functionally because homotypic aggregation of CD40 ligand-expressing B cells was inhibited by the CD40.Ig construct. Additionally, RNA and DNA synthesis as well as Ig production by polyclonally activated, highly purified peripheral B cells and a variety of B cell lines were inhibited significantly by the CD40.Ig construct. Finally, B cell lines expressing the CD40 ligand induced Ig production from resting normal B cells in a CD40-dependent manner. These results indicate that human B cells express a ligand for CD40 that is identical with that expressed by activated T cells and that the B cell-expressed CD40 ligand plays an important role in facilitating responses of activated B cells.

Gene regulation in inborn errors of immunity: Implications for gene therapy design and efficacy

“…149,150 Although CD40L is mainly associated with activated CD4 T cells, some expression has also been reported on other hematopoietic lineage cells, including B cells, NK, CD8 T cells, and basophils. [151][152][153][154] As such, its regulation is tightly controlled to be expressed in the appropriate cell(s) at the correct stage of development. Extensive research has been done to understand the complex nature of its regulation, and, likely, more is yet to be done.…”

“…A limitation of the study, however, is that it does not address the long-term function and stability of the geneedited cells in vivo, which is essential for evaluating the treatment's therapeutic effectiveness and safety. Moreover, the study only focuses on T cells, despite the expression of CD40L across a spectrum of hematopoietic cells such as activated B cells, platelets, monocytes, natural killer cells, mast cells, and basophils, [151][152][153][154] narrowing its breadth. Expanding this gene editing approach to target HSPCs could enhance its clinical relevance, even if it might result in diminished editing efficiency.…”

Enhanced Donor Antigen Presentation by B Cells Predicts Acute Cellular Rejection and Late Outcomes After Transplantation

“… 1 - 3 Activated B cells can also recruit other B cells to produce antibodies. 4 , 5 The CD40–CD154 interaction facilitates this communication within and between cell compartments and depends in part on the induction of CD40 on Tc and Th. 6 , 7 Reflecting the clinical import of these interactions, donor antigen–specific B cells, which express CD154 in lymphocyte co-culture, are enhanced during acute cellular rejection (ACR) after intestine transplantation and are strongly correlated with allospecific CD154 + Tc-memory cells (TcM), and with donor-specific anti-HLA antibodies (DSAs).…”