# Control of B cell development and effector functions by microRNA-142 > **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $425,000 ## Abstract Differentiation of B cell precursors into antibody-secreting B lymphocytes is a multi-stage process, and dysregulation of this intricate differentiation pathway is implicated in a wide range of immune diseases, from primary immunodeficiencies (PIDs) to autoimmune disorders such as systemic lupus erythematosus (SLE). An insufficient understanding of the molecular mechanisms that govern B cell biology is one of the critical barriers preventing development of impactful therapies against these B cell-mediated diseases. Control of gene expression by microRNAs (miRNAs) has recently emerged as a key mechanism that regulates B cell ontogenesis and effector responses. Thus, better insights into how individual miRNAs function in B cells may allow us to create novel, targeted strategies against immune diseases. The focus of this proposal is on miR-142. Using a loss-of-function genetic approach, we have established miR-142 as an essential, cell- intrinsic regulator of B cell physiology. miR-142 plays two contrasting roles in B cells − it attenuates B cell maturation, while promoting antibody responses. The objective of this proposal is to gain further insights into the role of miR-142 in B cell development and effector functions, and determine its mode of action in B cells. We have identified Wiskott-Aldrich syndrome like (WASL) gene as a bona fide target of miR-142 in B cells. WASL, like its close homolog WAS gene which is frequently mutated in patients with PIDs, encodes a multidomain protein that functions as a signaling hub that coordinates actin polymerization. Actin remodeling is important in the regulation of multiple aspects of B cell biology, including B cell maturation and antibody responses. Thus, our overall hypothesis is that miR-142, in part by targeting WASL, plays a crucial role in the regulation of B cell maturation and B cell effector responses. We will test our central hypothesis with three specific aims. In Aim 1, we will investigate the role of miR-142 in primary B cell development and define its mode of action. We will characterize B cell maturation defects in miR-142-/- mice, and link them to underlying molecular changes. Experiments proposed in Aim 2 will determine the impact of miR-142 deletion on B cell effector functions. Using mice with a conditional deletion of miR-142 in activated B cells, we will investigate the role of miR-142 in germinal center formation, immunoglobulin class-switching, and differentiation of long-term plasma cells. We will connect any observed defects in the physiology of miR-142-deficient effector B cells with changes in signaling and gene expression patterns. Finally, in Aim 3, we will define the role of WASL in miR- 142-mediated control of B cell maturation and effector responses by epistasis analysis. The proposed research is significant because it will advance our understanding of the post-transcriptional mechanisms that govern B cell development and humoral immune response. Moreover, our work is expect... ## Key facts - **NIH application ID:** 9929527 - **Project number:** 5R01AI125615-05 - **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE - **Principal Investigator:** Mark P Boldin - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $425,000 - **Award type:** 5 - **Project period:** 2016-06-15 → 2021-09-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9929527 ## Citation > US National Institutes of Health, RePORTER application 9929527, Control of B cell development and effector functions by microRNA-142 (5R01AI125615-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9929527. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*