Intraocular Differentiation of Effector B Cells in Uveitis

Johanna Rankenberg – Ophthalmology – University of Colorado School of Medicine; Catherine Nicholas – Ophthalmology – University of Colorado School of Medicine; Lynn Hassman – Ophthalmology – University of Colorado School of Medicine

Abstract Text: Uveitis encompasses a heterogeneous group of chronic inflammatory eye diseases. Although some patients benefit from B cell-targeted therapies, the precise role of B cells in uveitis remains elusive. To clarify their involvement, we conducted immune receptor profiling of B cells from the eyes and blood of uveitis patients and generated recombinant antibodies from selected ocular B cell receptors (BCRs) to investigate their antigen specificity.

Our analysis revealed that CD11c++ B cells and plasmablasts are significantly enriched and clonally expanded in ocular samples compared to blood. These expanded ocular clonotypes demonstrated intraconal diversity, predominantly between CD11c++ B cells and plasmablasts, highlighting local expansion and differentiation within the eye. Notably, ocular B cells were often class-switched and their BCRs exhibited somatic hypermutation, indicating prior antigen exposure. CD11c++ B cells and plasmablasts shared heavy chain V segment skewing and somatic hypermutation patterns, suggesting parallel antigen-specific recruitment or expansion.

Moreover, we identified convergent clonotypes across multiple patients, characterized by shared CDR3 sequence motifs, elevated somatic hypermutation levels, and reduced polyreactivity. This finding suggests that common antigens drive intraocular inflammation in uveitis patients.